Trial Outcomes & Findings for Alemtuzumab-Ofatumumab in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia (NCT NCT01361711)

NCT ID: NCT01361711

Last Updated: 2025-05-23

Results Overview

CR= Absence of clonal lymphocytes in the peripheral blood, significant lymphadenopathy, hepatomegaly or splenomegaly, and constitutional symptoms. Blood counts: Neutrophils ≥ 1,500/μL; Platelets \>100,000μL; Hemoglobin \> 11.0g/dL. Bone marrow normocellular for age, less than 30% of nucleated cells = lymphocytes. Lymphoid nodules absent. CRi= Fulfills CR but anemia or thrombocytopenia or neutropenia related to drug toxicity. PR= 2 criteria from group A and 1 from Group B. Group A: Decrease in the number of blood lymphocytes of 50% or more. Reduction in lymphadenopathy. No increase in any lymph node, and no new enlarged lymph node. A decrease in liver by at least 50% from baseline. Decrease in the size of the spleen by 50% or more. Reduction in marrow infiltrate or B-lymphoid nodules. Group B: Platelet counts \> than 100,000/μL or 50% better. Hemoglobin \> than 11.0g/dL or 50% better. Neutrophils\>1500/μL or 50% better. Criteria is continued in Analysis Population Description below...

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 53 participants
• Primary outcome timeframe: Range of responses between 8 weeks from initiation of treatment to 2 months post-treatment.
• Results posted on: 2025-05-23

Participant Flow

Opened for accrual on June 3, 2011 with goal of 60 patients. First patient started treatment June 13, 2011. Accrual was suspended Sep. 26, 2011 for safety analysis of the first 6 patients. The study opened May 4, 2012 for safety cohort of 6 more patients. Study was suspended July 23, 2012 for safety analysis, and opened again Feb 4, 2013. The study closed Sep 13, 2016 because the total accrual goal for Northwestern University was met.

Participant milestones

Measure	Alemtuzumab + Ofatumumab Alemtuzumab: Administered subcutaneously, 3 times per week for up to 18 weeks at a standard dose of 30mg (except for week 1 which will dose escalate from 3mg→10mg→30mg). Ofatumumab: Starting at week 3, administered intravenously on day 1 of every other week prior to alemtuzumab for a total of 8 doses. For week 3 (dose 1) ofatumumab will be given at a dose of 300mg; for weeks 5, 7, 9, 11, 13, 15, and 17 (doses 2-8) ofatumumab will be given at a dose of 2000mg. Toxicity was assessed after completion of the extended safety run-in period of the first 12 patients at an ofatumumab dose of 2000 mg for doses 2-8. Depending on the number of patients who experienced a dose limiting toxicity in the initial 2 safety cohorts, ofatumumab doses 2-8 could have been continued at 2000 mg or reduced to 1000 mg for subsequent patients. Based on the toxicity data of the first 12 patients, ofatumumab doses 2-8 were given at 2000 mg for doses 2-8 for all patients. Based on experience with the initial safety run-in cohort of 6 patients, early stopping is necessary to avoid over-treatment in patients who have achieved a complete remission early. As soon as a patient is determined to have achieved MRD- CR or CRi (per iwCLL2008 criteria), both alemtuzumab and ofatumumab will be stopped.
Trial Entry (Registration) STARTED	53
Trial Entry (Registration) Received Dose of Study Drug	52
Trial Entry (Registration) COMPLETED	52
Trial Entry (Registration) NOT COMPLETED	1
Week 9 Bone Marrow Response Assessment STARTED	52
Week 9 Bone Marrow Response Assessment COMPLETED	51
Week 9 Bone Marrow Response Assessment NOT COMPLETED	1
Continued Treatment After 9 Weeks STARTED	51
Continued Treatment After 9 Weeks COMPLETED	44
Continued Treatment After 9 Weeks NOT COMPLETED	7
Continued Treatment After 12 Weeks STARTED	44
Continued Treatment After 12 Weeks COMPLETED	41
Continued Treatment After 12 Weeks NOT COMPLETED	3
Completed Week 18 of Treatment STARTED	41
Completed Week 18 of Treatment COMPLETED	30
Completed Week 18 of Treatment NOT COMPLETED	11
10 Year Follow-up STARTED	52
10 Year Follow-up COMPLETED	2
10 Year Follow-up NOT COMPLETED	50

Reasons for withdrawal

Measure	Alemtuzumab + Ofatumumab Alemtuzumab: Administered subcutaneously, 3 times per week for up to 18 weeks at a standard dose of 30mg (except for week 1 which will dose escalate from 3mg→10mg→30mg). Ofatumumab: Starting at week 3, administered intravenously on day 1 of every other week prior to alemtuzumab for a total of 8 doses. For week 3 (dose 1) ofatumumab will be given at a dose of 300mg; for weeks 5, 7, 9, 11, 13, 15, and 17 (doses 2-8) ofatumumab will be given at a dose of 2000mg. Toxicity was assessed after completion of the extended safety run-in period of the first 12 patients at an ofatumumab dose of 2000 mg for doses 2-8. Depending on the number of patients who experienced a dose limiting toxicity in the initial 2 safety cohorts, ofatumumab doses 2-8 could have been continued at 2000 mg or reduced to 1000 mg for subsequent patients. Based on the toxicity data of the first 12 patients, ofatumumab doses 2-8 were given at 2000 mg for doses 2-8 for all patients. Based on experience with the initial safety run-in cohort of 6 patients, early stopping is necessary to avoid over-treatment in patients who have achieved a complete remission early. As soon as a patient is determined to have achieved MRD- CR or CRi (per iwCLL2008 criteria), both alemtuzumab and ofatumumab will be stopped.
Trial Entry (Registration) Patient did not meet Protocol criteria for trial entry	1
Week 9 Bone Marrow Response Assessment Complete Remission in Week 8	1
Continued Treatment After 9 Weeks Complete Remission in Week 9	7
Continued Treatment After 12 Weeks Complete Remission in Week 12	2
Continued Treatment After 12 Weeks Progressive Disease at Week 11	1
Completed Week 18 of Treatment Complete Remission	2
Completed Week 18 of Treatment Other	9
10 Year Follow-up Still in follow-up	22
10 Year Follow-up Death	7
10 Year Follow-up Developed new cancer	1
10 Year Follow-up Lost to Follow-up	2
10 Year Follow-up New treatment started	6
10 Year Follow-up Progressive Disease and New treatment started	11
10 Year Follow-up Progressive Disease	1

Baseline Characteristics

Alemtuzumab-Ofatumumab in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Measure	Alemtuzumab + Ofatumumab n=52 Participants Alemtuzumab: Administered subcutaneously, 3 times per week for up to 18 weeks at a standard dose of 30mg (except for week 1 which will dose escalate from 3mg→10mg→30mg). Ofatumumab: Starting at week 3, administered intravenously on day 1 of every other week prior to alemtuzumab for a total of 8 doses. For week 3 (dose 1) ofatumumab will be given at a dose of 300mg; for weeks 5, 7, 9, 11, 13, 15, and 17 (doses 2-8) ofatumumab will be given at a dose of 2000mg. Toxicity was assessed after completion of the extended safety run-in period of the first 12 patients at an ofatumumab dose of 2000 mg for doses 2-8. Depending on the number of patients who experienced a dose limiting toxicity in the initial 2 safety cohorts, ofatumumab doses 2-8 could have been continued at 2000 mg or reduced to 1000 mg for subsequent patients. Based on the toxicity data of the first 12 patients, ofatumumab doses 2-8 were given at 2000 mg for doses 2-8 for all patients. biopsy: Correlative studies
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=5 Participants
Age, Categorical >=65 years	24 Participants n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	50 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Sweden	20 participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants

PRIMARY outcome

Timeframe: Range of responses between 8 weeks from initiation of treatment to 2 months post-treatment.

Population: Criteria from Outcome Measure Description cont. MRD=Bone marrow with less than one CLL cell per 10,000 leukocytes. To qualify as a PD: at least two of the criteria of in Group A, plus one of the criteria in Group B, must be met. Group A: An increase ≥ 50% of: lymphadenopathy, hepatomegaly, or splenomegaly. An increase ≥ 50% over baseline in blood lymphocytes. Group B: Platelet count decrease of ≥ 50% from baseline secondary to CLL, Hemoglobin decrease of \> 2g/dl from baseline secondary to CLL.

CR= Absence of clonal lymphocytes in the peripheral blood, significant lymphadenopathy, hepatomegaly or splenomegaly, and constitutional symptoms. Blood counts: Neutrophils ≥ 1,500/μL; Platelets >100,000μL; Hemoglobin > 11.0g/dL. Bone marrow normocellular for age, less than 30% of nucleated cells = lymphocytes. Lymphoid nodules absent. CRi= Fulfills CR but anemia or thrombocytopenia or neutropenia related to drug toxicity. PR= 2 criteria from group A and 1 from Group B. Group A: Decrease in the number of blood lymphocytes of 50% or more. Reduction in lymphadenopathy. No increase in any lymph node, and no new enlarged lymph node. A decrease in liver by at least 50% from baseline. Decrease in the size of the spleen by 50% or more. Reduction in marrow infiltrate or B-lymphoid nodules. Group B: Platelet counts > than 100,000/μL or 50% better. Hemoglobin > than 11.0g/dL or 50% better. Neutrophils>1500/μL or 50% better. Criteria is continued in Analysis Population Description below...

Outcome measures

Measure	Alemtuzumab + Ofatumumab n=52 Participants Alemtuzumab: Administered subcutaneously, 3 times per week for up to 18 weeks at a standard dose of 30mg (except for week 1 which will dose escalate from 3mg→10mg→30mg). Ofatumumab: Starting at week 3, administered intravenously on day 1 of every other week prior to alemtuzumab for a total of 8 doses. For week 3 (dose 1) ofatumumab will be given at a dose of 300mg; for weeks 5, 7, 9, 11, 13, 15, and 17 (doses 2-8) ofatumumab will be given at a dose of 2000mg. Toxicity was assessed after completion of the extended safety run-in period of the first 12 patients at an ofatumumab dose of 2000 mg for doses 2-8. Depending on the number of patients who experienced a dose limiting toxicity in the initial 2 safety cohorts, ofatumumab doses 2-8 could have been continued at 2000 mg or reduced to 1000 mg for subsequent patients. Based on the toxicity data of the first 12 patients, ofatumumab doses 2-8 were given at 2000 mg for doses 2-8 for all patients. biopsy: Correlative studies
Best Response as Defined by the iwCLL2008 (International Workshop on Chronic Lymphocytic Leukemia 2008) Complete Remission (CR), Minimal Residual Disease (MRD) Negative	18 Participants
Best Response as Defined by the iwCLL2008 (International Workshop on Chronic Lymphocytic Leukemia 2008) Complete Remission (CR), Minimal Residual Disease (MRD) positive	2 Participants
Best Response as Defined by the iwCLL2008 (International Workshop on Chronic Lymphocytic Leukemia 2008) Complete Remission, MRD status unknown	3 Participants
Best Response as Defined by the iwCLL2008 (International Workshop on Chronic Lymphocytic Leukemia 2008) Complete Remission with Incomplete Marrow Recovery (CRi)	2 Participants
Best Response as Defined by the iwCLL2008 (International Workshop on Chronic Lymphocytic Leukemia 2008) Partial Remission (PR)	26 Participants
Best Response as Defined by the iwCLL2008 (International Workshop on Chronic Lymphocytic Leukemia 2008) Progressive Disease (PD)	1 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Survival rates will be calculated for progression-free survival (PFS), therapy-free survival (TFS), and overall survival (OS).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 1, 3, 5, 7, 9, 11, 13, 15, and 17

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline and over 18 weeks

Clinical outcomes (such as response, PFS and TFS) will be correlated with pre-treatment clinical and biological characteristics(such as Rai staging, presence of bulky lymph nodes, cytogenetics by FISH, CD38, ZAP70 and IgVH mutation status).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline and over 18 weeks

Response and survival rates will be compared between the two studies.

Outcome measures

Outcome data not reported

Adverse Events

Alemtuzumab + Ofatumumab

Serious events: 20 serious events

Other events: 52 other events

Deaths: 6 deaths

Serious adverse events

Measure	Alemtuzumab + Ofatumumab n=52 participants at risk Alemtuzumab: Administered subcutaneously, 3 times per week for up to 18 weeks at a standard dose of 30mg (except for week 1 which will dose escalate from 3mg→10mg→30mg). Ofatumumab: Starting at week 3, administered intravenously on day 1 of every other week prior to alemtuzumab for a total of 8 doses. For week 3 (dose 1) ofatumumab will be given at a dose of 300mg; for weeks 5, 7, 9, 11, 13, 15, and 17 (doses 2-8) ofatumumab will be given at a dose of 2000mg. Toxicity was assessed after completion of the extended safety run-in period of the first 12 patients at an ofatumumab dose of 2000 mg for doses 2-8. Depending on the number of patients who experienced a dose limiting toxicity in the initial 2 safety cohorts, ofatumumab doses 2-8 could have been continued at 2000 mg or reduced to 1000 mg for subsequent patients. Based on the toxicity data of the first 12 patients, ofatumumab doses 2-8 were given at 2000 mg for doses 2-8 for all patients. Based on experience with the initial safety run-in cohort of 6 patients, early stopping is necessary to avoid over-treatment in patients who have achieved a complete remission early. As soon as a patient is determined to have achieved MRD- CR or CRi (per iwCLL2008 criteria), both alemtuzumab and ofatumumab will be stopped.
Infections and infestations Infection	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Abnormal Platelets	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Fever	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Febrile neutropenia	9.6% 5/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations CMV infection	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations MRSA Bacteremia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Neutropenic fever	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse Large B-Cell Lymphoma	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Renal and urinary disorders Acute kidney injury	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Cardiac disorders Sinus tachycardia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Meningitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Immune system disorders Allergic reaction	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations CMV positive	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Erythema multiforme	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Lung infection	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.

Other adverse events

Measure	Alemtuzumab + Ofatumumab n=52 participants at risk Alemtuzumab: Administered subcutaneously, 3 times per week for up to 18 weeks at a standard dose of 30mg (except for week 1 which will dose escalate from 3mg→10mg→30mg). Ofatumumab: Starting at week 3, administered intravenously on day 1 of every other week prior to alemtuzumab for a total of 8 doses. For week 3 (dose 1) ofatumumab will be given at a dose of 300mg; for weeks 5, 7, 9, 11, 13, 15, and 17 (doses 2-8) ofatumumab will be given at a dose of 2000mg. Toxicity was assessed after completion of the extended safety run-in period of the first 12 patients at an ofatumumab dose of 2000 mg for doses 2-8. Depending on the number of patients who experienced a dose limiting toxicity in the initial 2 safety cohorts, ofatumumab doses 2-8 could have been continued at 2000 mg or reduced to 1000 mg for subsequent patients. Based on the toxicity data of the first 12 patients, ofatumumab doses 2-8 were given at 2000 mg for doses 2-8 for all patients. Based on experience with the initial safety run-in cohort of 6 patients, early stopping is necessary to avoid over-treatment in patients who have achieved a complete remission early. As soon as a patient is determined to have achieved MRD- CR or CRi (per iwCLL2008 criteria), both alemtuzumab and ofatumumab will be stopped.
Gastrointestinal disorders Abdominal cramping	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Abdominal discomfort	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Abdominal distension	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Abdominal pain	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Abnormal C-reactive protein levels	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Abnormal Hemoglobin count	84.6% 44/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Abnormal neutrophil count	84.6% 44/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Abnormal platelet count	82.7% 43/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Abscess	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Actinic keratoses	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Renal and urinary disorders Acute kidney injury	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Alanine aminotransferase increased	26.9% 14/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Alkaline phosphatase increased	15.4% 8/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Immune system disorders Allergic reaction	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Anemia	9.6% 5/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Anorexia	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Psychiatric disorders Anxiety	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Appendicitis	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Arthritis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Aspartate aminotransferase increased	46.2% 24/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Cardiac disorders Atrial fibrillation	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Immune system disorders Autoimmune disorder	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Back pain	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Basal Cell Carcinoma Recurrence	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Reproductive system and breast disorders Benign prostatic hyperplasia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Blood bilirubin increased	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Eye disorders Blurred vision	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Bone pain	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Borderline diabetes	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Eye disorders Brown tint to vision	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Ear and labyrinth disorders Cerumen Impaction	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Cherry angiomas	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Cardiac disorders Chest pain	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Chest tightness	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Chills	25.0% 13/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations High cholesterol	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations CMV reactivation	34.6% 18/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations CMV Infection	21.2% 11/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Concentration impairment	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Constipation	17.3% 9/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Cardiac disorders Coronary artery disease	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Cough	11.5% 6/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Creatinine increased	30.8% 16/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Immune system disorders Cytokine release syndrome	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Decrease absolute CD3+	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Decrease absolute CD3+CD8+	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Decrease absolute CD3+CD4+	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations decreased hematocrit	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Decreased B cell %	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Decreased IgG	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Decreased IgA	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Decreased IgM	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Renal and urinary disorders Decreased urination	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Psychiatric disorders Depression	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Diabetes	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Diabetes Mellitus	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Diabetic ketoacidosis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Diarrhea	28.8% 15/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Diffuse Large B-Cell Lymphoma	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Diverticulosis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Dizziness	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Eye disorders Double vision	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Dry mouth	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Dry skin	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Dyspepsia	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Easy bruising	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Edema limbs	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Elevated LDH	13.5% 7/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Elevated neutrophils	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Immune system disorders Elevated Quantitative IgG	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Endocrine disorders Enlarged adrenal glands	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Enlarged lymph node in left groin	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Reproductive system and breast disorders Enlargement of prostate gland	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Reproductive system and breast disorders Erectile dysfunction	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Erythema multiforme	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Erythematous Rash	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Fatigue	65.4% 34/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Febrile neutropenia	17.3% 9/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Fever	67.3% 35/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Flu like symptoms	23.1% 12/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Vascular disorders Flushing	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Gait disturbance	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Gastritis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Gastroesophageal reflux disease	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Gastrointestinal pain	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Genital herpes	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders guttate psoriasis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Headache	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Headache	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Hemolysis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Hemorrhoids	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Hepatobiliary disorders Hepatitis B positive	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Hiccups	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Hip pain	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Hoarseness	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypercalcemia	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hyperglycemia	48.1% 25/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hyperkalemia	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hyperlipidemia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypermagnesemia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Vascular disorders Hypertension	17.3% 9/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypertriglyceridemia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hyperuricemia	9.6% 5/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypoalbuminemia	23.1% 12/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypocalcemia	11.5% 6/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Immune system disorders Hypogammaglobulinemia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypoglycemia	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypokalemia	11.5% 6/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypomagnesemia	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hyponatremia	17.3% 9/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders Hypophosphatemia	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Hyposmia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Vascular disorders Hypotension	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Endocrine disorders Hypothyroidism	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations IgM paraprotein	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Increased C-reactive protein.	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Infusion related reaction	55.8% 29/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Infusion site extravasation	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Injection site reaction	90.4% 47/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Psychiatric disorders Insomnia	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Iron deficiency	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Itchiness in throat	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Eye disorders Keratitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Metabolism and nutrition disorders lack of vitamin B12	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Surgical and medical procedures Laparoscopic appendectomy	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Cardiac disorders Left branch bundle block	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Left lumbar spasm	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Legionella Pneumonia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Leukocytosis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Lightheadedness	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Lower leg lesions	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Lung infection	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Lymphocyte count decreased	46.2% 24/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Lymphocyte count increased	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Malaise	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Memory impairment	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Meningitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations MRSA Bacteremia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Mucosal infection	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Mucositis oral	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Muscle weakness trunk	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Myalgia	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Nausea	13.5% 7/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Neck pain	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Neutropenia	17.3% 9/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Neutrophil count decreased	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Night Sweats	21.2% 11/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Cardiac disorders Nonspecific T Wave Abnormalities	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Oral pain	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
General disorders Pain	11.5% 6/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Pain in extremity	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Pain in shoulder	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Pain of skin	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Cardiac disorders Palpitations	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Peripheral motor neuropathy	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Peripheral neuropathy in feet	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Peripheral sensory neuropathy	15.4% 8/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders perivascular dermatitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Petechiae on upper abdomen	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations pneumonia, community acquired	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) polyps	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Renal and urinary disorders Pressure with urination	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Renal and urinary disorders Proteinuria	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Pruritus	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Vascular disorders Pulmonary emboli	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Rash	15.4% 8/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders redness of the skin with scaling	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Renal and urinary disorders Benign prostatic hyperplasia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Restless legs syndrome	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Rhinitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Ringing in ears	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Rising PSA	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Scalp psoriasis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Seborrheic dermatitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Seborrheic keratoses	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Sensory numbness	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Cardiac disorders Sinus tachycardia	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Sinusitis	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Skin infection	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Skin tear on right buttock	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Respiratory, thoracic and mediastinal disorders Sore throat	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Spongiotic Dermatitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Subacute Spongiotic Dermatitis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Sun damaged skin	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Surgical and medical procedures Surgery for testicular varicose	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) surgery to remove two small basiliom	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Sweating	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Reproductive system and breast disorders Testicular pain	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Thrombocytopenia	11.5% 6/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Vascular disorders Thromboembolic event	9.6% 5/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Tinea pedis	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Tingling in fingertips to elbows	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Nervous system disorders Tingling in lips	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Skin and subcutaneous tissue disorders Tingling in the face	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Surgical and medical procedures Tonsillectomy	3.8% 2/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Upper respiratory infection	7.7% 4/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Urinary tract infection	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Reproductive system and breast disorders Vaginal Atrophy	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Infections and infestations Vaginal infection	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Gastrointestinal disorders Vomiting	5.8% 3/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Weight gain	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations Weight loss	11.5% 6/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Investigations White blood cell decreased	67.3% 35/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.
Musculoskeletal and connective tissue disorders Worsening of gout	1.9% 1/52 • Adverse events were collected over a four year period. Each patient was followed from the time of treatment, and during treatment up to 18 weeks. Adverse events were collected up to 60 days post-therapy. Serious adverse events (SAEs) were collected for one year after treatment discontinuation or until the initiation of second-line therapy.

Additional Information

Shuo Ma, MD, PhD

Northwestern University

Phone: 312-908-5250

Email: shuo-ma@northwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place