Trial Outcomes & Findings for Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma (NCT NCT01856192)

Last Updated: 2025-11-10

Results Overview

Progression-free survival is defined as the time from randomization to disease progression, new primary of the same type or death, whichever occurs first. Progressive disease is defined as: * Appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size. * \>= 50% increase from nadir in the sum of the product of the diameters of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions. * \>= 50% increase in the longest diameter of any single previously identified node or extranodal mass \> 1 cm in its short axis. * Lesions should be PET positive unless the lesion is too small to be detected with current PET systems. * Measurable extranodal disease should be assessed in a manner similar to that for nodal disease. 3-year progression-free survival rate was calculated using Kaplan-Meier method.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

349 participants

Primary outcome timeframe

Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10, 3-year PFS rate reported

Results posted on

2025-11-10

Participant Flow

Between August 2013 and January 2017, 349 patients were enrolled on this study.

Participant milestones

Participant milestones
Measure	Arm A (R2CHOP) Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm B (RCHOP) Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	173	176
Overall Study Treated Patients	166	171
Overall Study Evaluable Patients (Eligible and Treated)	145	135
Overall Study COMPLETED	124	116
Overall Study NOT COMPLETED	49	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (R2CHOP) Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm B (RCHOP) Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Adverse Event	12	4
Overall Study Alternative therapy	0	3
Overall Study Death	3	5
Overall Study Lack of Efficacy	0	5
Overall Study Withdrawal by Subject	1	1
Overall Study Other diseases	1	0
Overall Study Never started treatment	7	5
Overall Study Path ineligible	20	34
Overall Study Non-path ineligible	2	2
Overall Study Physician Decision	1	1
Overall Study Suspicion of progressive disease	1	0
Overall Study Non-compliance	1	0

Baseline Characteristics

Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (R2CHOP) n=145 Participants Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm B (RCHOP) n=135 Participants Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Total n=280 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=20 Participants	8 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	137 Participants n=5 Participants	125 Participants n=20 Participants	262 Participants n=40 Participants
Age, Continuous	67 years n=5 Participants	66 years n=20 Participants	66 years n=40 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	59 Participants n=20 Participants	110 Participants n=40 Participants
Sex: Female, Male Male	94 Participants n=5 Participants	76 Participants n=20 Participants	170 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	5 Participants n=20 Participants	10 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	2 Participants n=20 Participants	8 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	10 Participants n=20 Participants	16 Participants n=40 Participants
Race (NIH/OMB) White	128 Participants n=5 Participants	118 Participants n=20 Participants	246 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	5 Participants n=20 Participants	10 Participants n=40 Participants

PRIMARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10, 3-year PFS rate reported

Population: Evaluable (eligible and treated) patients

Outcome measures

Outcome measures
Measure	Arm B (RCHOP) n=135 Participants Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm A (R2CHOP) n=145 Participants Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
3-year Progression-free Survival Rate	0.615 proportion of participants Interval 0.562 to 0.674	0.727 proportion of participants Interval 0.678 to 0.779

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10

Population: Evaluable (eligible and treated) patients

Response is defined as complete response (CR) or partial response (PR) CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms PR: * \>=50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses * No increase in the size of other nodes, liver or spleen * Bone marrow assessment is irrelevant for determination of a PR if the sample was positive prior to treatment. However, if positive, the cell type should be specified * No new sites of disease * The post-treatment PET should be positive at any previously involved sites * For variably FDG-avid lymphomas/FDG-avidity unknown, without a pretreatment PET scan, or if a pretreatment PET scan was negative, CT scan criteria should be used * Patients with a CR and persistent morphologic bone marrow involvement * Patients with bone marrow involved before therapy and a clinical CR but no bone marrow assessment after treatment

Outcome measures

Outcome measures
Measure	Arm B (RCHOP) n=135 Participants Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm A (R2CHOP) n=145 Participants Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Response	0.92 proportion of participants Interval 0.87 to 0.95	0.97 proportion of participants Interval 0.94 to 0.99

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10

Population: Evaluable (eligible and treated) patients

Complete response is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.

Outcome measures

Outcome measures
Measure	Arm B (RCHOP) n=135 Participants Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm A (R2CHOP) n=145 Participants Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Complete Response	0.68 proportion of participants Interval 0.61 to 0.75	0.73 proportion of participants Interval 0.66 to 0.79

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10

Population: Evaluable (eligible and treated) patients

Overall survival is defined as time from randomization to death or date last known alive. Overall survival rate at 3 years was calculated using the method of Kaplan Meier.

Outcome measures

Outcome measures
Measure	Arm B (RCHOP) n=135 Participants Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm A (R2CHOP) n=145 Participants Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Survival Rate at 3 Years	0.751 proportion of participants Interval 0.681 to 0.829	0.826 proportion of participants Interval 0.765 to 0.892

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline, every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10

* To evaluate the association between the binary score of baseline SUV and PFS. * To evaluate the association between the binary score of % change in standard uptake value (SUVs) from PET3 to baseline and PFS.

Outcome measures

Outcome data not reported

Adverse Events

Arm A (R2CHOP)

Serious events: 128 serious events

Other events: 164 other events

Deaths: 36 deaths

Arm B (RCHOP)

Serious events: 117 serious events

Other events: 164 other events

Deaths: 43 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Biostatistics Center

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm A (R2CHOP) n=166 participants at risk Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm B (RCHOP) n=171 participants at risk Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Ear and labyrinth disorders Tinnitus	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Anemia	29.5% 49/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	20.5% 35/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Febrile neutropenia	25.3% 42/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	12.3% 21/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Atrial fibrillation	1.2% 2/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Heart failure	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Left ventricular systolic dysfunction	1.2% 2/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.8% 3/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Pericarditis	0.00% 0/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Restrictive cardiomyopathy	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Sinus bradycardia	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Cardiac disorders - Other, specify	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Edema limbs	0.00% 0/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Fatigue	10.2% 17/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.4% 11/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Fever	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Infusion related reaction	1.2% 2/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Pruritus	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.8% 3/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Toxic epidermal necrolysis	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Abdominal pain	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Colitis	0.00% 0/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Constipation	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Diarrhea	6.0% 10/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Enterocolitis	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastric hemorrhage	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastric perforation	0.00% 0/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Ileal obstruction	0.00% 0/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Mucositis oral	3.0% 5/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.8% 3/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Nausea	1.2% 2/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.2% 2/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Small intestinal obstruction	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Small intestinal perforation	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Vomiting	1.2% 2/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Abdominal infection	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Anorectal infection	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Enterocolitis infectious	0.60% 1/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Lung infection	6.6% 11/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.7% 8/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Pleural infection	0.00% 0/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Sepsis	6.6% 11/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	5.8% 10/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.

Other adverse events
Measure	Arm A (R2CHOP) n=166 participants at risk Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone PO on days 1-5; and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm B (RCHOP) n=171 participants at risk Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	86.7% 144/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	78.4% 134/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Chills	10.2% 17/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.4% 11/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Edema limbs	23.5% 39/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	12.9% 22/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Fatigue	75.9% 126/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	78.9% 135/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Fever	14.5% 24/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	11.1% 19/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Infusion related reaction	6.6% 11/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.5% 6/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Pain	3.0% 5/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	5.8% 10/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Alopecia	39.8% 66/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	40.4% 69/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Dry skin	6.0% 10/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 1/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Pruritus	7.2% 12/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.5% 6/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Rash maculo-papular	9.6% 16/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.2% 2/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Abdominal pain	9.6% 16/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	7.6% 13/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Constipation	49.4% 82/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	42.7% 73/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Diarrhea	34.9% 58/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	24.6% 42/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Dry mouth	8.4% 14/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.9% 5/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Dyspepsia	4.8% 8/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	8.8% 15/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Mucositis oral	19.9% 33/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	20.5% 35/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Nausea	45.8% 76/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	28.1% 48/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Vomiting	19.3% 32/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	10.5% 18/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	5.4% 9/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.5% 6/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Alanine aminotransferase increased	7.2% 12/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	7.6% 13/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Alkaline phosphatase increased	9.0% 15/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.1% 7/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Aspartate aminotransferase increased	7.8% 13/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	7.0% 12/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Blood bilirubin increased	10.2% 17/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.9% 5/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Creatinine increased	4.8% 8/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.4% 11/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Lymphocyte count decreased	31.3% 52/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	32.7% 56/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Neutrophil count decreased	35.5% 59/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	23.4% 40/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Platelet count decreased	44.6% 74/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	38.0% 65/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Weight loss	16.9% 28/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	15.2% 26/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations White blood cell decreased	36.1% 60/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	19.9% 34/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Anorexia	28.3% 47/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	26.9% 46/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Dehydration	5.4% 9/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	9.9% 17/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyperglycemia	12.7% 21/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	9.9% 17/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypoalbuminemia	20.5% 34/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	14.6% 25/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypocalcemia	11.4% 19/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	7.0% 12/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypokalemia	16.9% 28/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	11.1% 19/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypomagnesemia	7.2% 12/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.3% 4/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyponatremia	12.7% 21/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	10.5% 18/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	15.1% 25/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	11.7% 20/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Myalgia	7.8% 13/166 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	5.3% 9/171 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 10 years. Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.