Trial Outcomes & Findings for A Study to Evaluate Safety, Efficacy and Pharmacokinetics of Rituximab (MabThera/Rituxan) in Participants With Diffuse Large B Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL) (NCT NCT01889069)

Last Updated: 2020-08-13

Results Overview

AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab administration and which were considered related to study drug. AARs included infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof. Grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

159 participants

Primary outcome timeframe

Baseline up to 54 months

Results posted on

2020-08-13

Participant Flow

The study was conducted at 37 investigational centers in Italy.

Total overall participants enrolled in the study was 159, however for the subject disposition and baseline characteristics the enrolled was 158 as one participant discontinued the study prior to treatment.

Participant milestones

Participant milestones
Measure	Subcutaneous (SC) Rituximab Participants will receive at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Overall Study STARTED	158
Overall Study COMPLETED	113
Overall Study NOT COMPLETED	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Subcutaneous (SC) Rituximab Participants will receive at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Overall Study Death	18
Overall Study Progression of Disease	14
Overall Study Lost to Follow-up	6
Overall Study Other	4
Overall Study Consent Withdrawal	3

Baseline Characteristics

A Study to Evaluate Safety, Efficacy and Pharmacokinetics of Rituximab (MabThera/Rituxan) in Participants With Diffuse Large B Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maximum of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Total n=158 Participants Total of all reporting groups
Age, Continuous Intent-to-Treat Population	59.7 years STANDARD_DEVIATION 12.70 • n=5 Participants	57.8 years STANDARD_DEVIATION 9.92 • n=7 Participants	58.7 years STANDARD_DEVIATION 11.28 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	44 Participants n=7 Participants	72 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	42 Participants n=7 Participants	86 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants	72 Participants n=7 Participants	131 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 54 months

Population: Safety Population included all enrolled participants who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With Administration-Associated Reactions (AAR) At least One AAR	4.2 Percentage of Participants	8.1 Percentage of Participants	6.3 Percentage of Participants
Percentage of Participants With Administration-Associated Reactions (AAR) At Least One AAR Grade ≥3	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Administration-Associated Reactions (AAR) Cutaneous and Soft Tissue AARs (Localized)	1.4 Percentage of Participants	8.1 Percentage of Participants	5.1 Percentage of Participants
Percentage of Participants With Administration-Associated Reactions (AAR) Cutaneous and Soft Tissue AARs (Non-Localized)	2.8 Percentage of Participants	0 Percentage of Participants	1.3 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline up to 54 months

Population: Safety Population included all enrolled participants who received at least one dose of study medication.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. Grading was completed according to the CTCAE, version 4.0.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs)	51.4 Percentage of Participants	43.0 Percentage of Participants	46.8 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline up to 54 months

Population: Safety Population included all enrolled participants who received at least one dose of study medication.

Grading of IIRRs was completed according to the CTCAE, version 4.0.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs)	0 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline up to 54 months

Population: Safety Population included all enrolled participants who received at least one dose of study medication.

SAE was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events	36.1 Percentage of Participants	26.7 Percentage of Participants	31.0 Percentage of Participants

SECONDARY outcome

Timeframe: Day 1 up to first occurrence of progression or relapse, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first (up to maximum 54 months)

Population: ITT population included all enrolled participants who received at least one dose of the study drug.

EFS was defined as the time from first dose of rituximab to first occurrence of progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurred first.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria	29.2 Percentage of Participants	22.1 Percentage of Participants	25.3 Percentage of Participants

SECONDARY outcome

Timeframe: Day 1 up to first occurrence of progression or relapse, or death, whichever occurs first (up to maximum 54 months)

Population: ITT population included all enrolled participants who received at least one dose of the study drug.

PFS was defined as the time from first dose of rituximab to the first occurrence of disease progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or death from any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria	29.2 Percentage of Participants	22.1 Percentage of Participants	25.3 Percentage of Participants

SECONDARY outcome

Timeframe: Day 1 until death (up to maximum 54 months)

Population: ITT population included all enrolled participants who received at least one dose of the study drug.

OS was defined as the time from first dose of rituximab to death from any cause.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With Overall Survival (OS)	19.4 Percentage of Participants	4.7 Percentage of Participants	11.4 Percentage of Participants

SECONDARY outcome

Timeframe: From 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occurs first (up to maximum 54 months) (end of Induction period = up to 8 months)

Population: ITT population included all enrolled participants who received at least one dose of the study drug.

DFS assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occured first.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria	21.7 Percentage of Participants	25.6 Percentage of Participants	23.5 Percentage of Participants

SECONDARY outcome

Timeframe: At 4 to 8 weeks after end of Induction period (end of Induction period = up to 8 months)

Population: ITT population included all enrolled participants who received at least one dose of the study drug.

Complete response required: 1) the complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities, 2) all lymph nodes and nodal masses had regressed to normal size, 3) the spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and not be palpable on physical examination and 4) if the bone marrow was involved by lymphoma before treatment, the infiltrate was cleared on repeat bone marrow aspirate and biopsy of the same site. CR/unconfirmed (CRu) included those patients who fulfilled criteria 1 and 3 above as well as 1) a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that regressed by more than 75% in the SPD and 2) indeterminate bone marrow. Response was assessed according to the IWG response criteria.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab n=158 Participants Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Percentage of Participants With Complete Response (CR) According to IWG Response Criteria	65.2 Percentage of Participants Interval 52.4 to 76.5	67.9 Percentage of Participants Interval 53.7 to 80.1	66.4 Percentage of Participants Interval 57.2 to 74.8

SECONDARY outcome

Timeframe: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1

Population: The number analyzed includes participants who were evaluable at each timepoint.

FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Pharmacokinetic (PK) data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=31 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
FL: Plasma Trough Concentrations of Rituximab Cycle 2 Predose	55.49 micrograms per millilitre (ug/mL) Standard Deviation 64.275	—	—
FL: Plasma Trough Concentrations of Rituximab Cycle 3 Predose	119.50 micrograms per millilitre (ug/mL) Standard Deviation 139.606	—	—
FL: Plasma Trough Concentrations of Rituximab Cycle 4 Predose	157.25 micrograms per millilitre (ug/mL) Standard Deviation 132.583	—	—
FL: Plasma Trough Concentrations of Rituximab Cycle 5 Predose	7.60 micrograms per millilitre (ug/mL) Standard Deviation NA Standard deviation could not be calculated from data for a single participant.	—	—
FL: Plasma Trough Concentrations of Rituximab Baseline	90.88 micrograms per millilitre (ug/mL) Standard Deviation 107.089	—	—
FL: Plasma Trough Concentrations of Rituximab Cycle 8 Predose	201.56 micrograms per millilitre (ug/mL) Standard Deviation 372.609	—	—

SECONDARY outcome

Timeframe: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1

Population: The overall geometric LS mean plasma trough concentrations of rituximab in participants with FL in the pharmacokinetic (PK) population. The number analyzed includes participants who were evaluable at each timepoint.

FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=31 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
FL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab	61.01 micrograms per millilitre (ug/mL) Interval 42.49 to 87.61	—	—

SECONDARY outcome

Timeframe: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1

Population: FL participants with Complete Response/Complete Response Unconfirmed (CR/CRu). The number analyzed includes participants who were evaluable at each timepoint.

FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=20 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 2 Predose	48.86 micrograms per millilitre (ug/mL) Standard Deviation 57.640	—	—
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 3 Predose	156.33 micrograms per millilitre (ug/mL) Standard Deviation 193.753	—	—
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 4 Predose	200.33 micrograms per millilitre (ug/mL) Standard Deviation 123.411	—	—
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 5 Predose	7.60 micrograms per millilitre (ug/mL) Standard Deviation NA Standard deviation could not be calculated from data for a single participant.	—	—
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Baseline	97.90 micrograms per millilitre (ug/mL) Standard Deviation 118.897	—	—
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 8 Predose	284.08 micrograms per millilitre (ug/mL) Standard Deviation 504.113	—	—

SECONDARY outcome

Timeframe: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1

Population: The number analyzed includes participants who were evaluable at each timepoint.

DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=36 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
DLBCL: Plasma Concentrations of Rituximab Cycle 2 Predose	42.53 micrograms per millilitre (ug/mL) Standard Deviation 49.637	—	—
DLBCL: Plasma Concentrations of Rituximab Cycle 3 Predose	88.92 micrograms per millilitre (ug/mL) Standard Deviation 92.790	—	—
DLBCL: Plasma Concentrations of Rituximab Cycle 4 Predose	110.50 micrograms per millilitre (ug/mL) Standard Deviation 101.116	—	—
DLBCL: Plasma Concentrations of Rituximab Cycle 5 Predose	100.20 micrograms per millilitre (ug/mL) Standard Deviation 44.483	—	—
DLBCL: Plasma Concentrations of Rituximab Baseline	92.92 micrograms per millilitre (ug/mL) Standard Deviation 114.466	—	—
DLBCL: Plasma Concentrations of Rituximab Cycle 7 Predose	141.44 micrograms per millilitre (ug/mL) Standard Deviation 122.314	—	—
DLBCL: Plasma Concentrations of Rituximab Cycle 7 Day 7	348.81 micrograms per millilitre (ug/mL) Standard Deviation 490.785	—	—
DLBCL: Plasma Concentrations of Rituximab Cycle 7 Day 14	226.40 micrograms per millilitre (ug/mL) Standard Deviation 136.729	—	—
DLBCL: Plasma Concentrations of Rituximab Cycle 8 Predose	117.61 micrograms per millilitre (ug/mL) Standard Deviation 89.394	—	—

SECONDARY outcome

Timeframe: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 pre-dose on Day 1

Population: The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=36 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
DLBCL: Plasma Trough Concentrations of Rituximab Cycle 2 Predose	42.53 micrograms per millilitre (ug/mL) Standard Deviation 49.637	—	—
DLBCL: Plasma Trough Concentrations of Rituximab Cycle 3 Predose	88.92 micrograms per millilitre (ug/mL) Standard Deviation 92.790	—	—
DLBCL: Plasma Trough Concentrations of Rituximab Cycle 4 Predose	110.50 micrograms per millilitre (ug/mL) Standard Deviation 101.116	—	—
DLBCL: Plasma Trough Concentrations of Rituximab Cycle 5 Predose	100.20 micrograms per millilitre (ug/mL) Standard Deviation 44.483	—	—
DLBCL: Plasma Trough Concentrations of Rituximab Baseline	92.92 micrograms per millilitre (ug/mL) Standard Deviation 114.466	—	—
DLBCL: Plasma Trough Concentrations of Rituximab Cycle 7 Predose	141.44 micrograms per millilitre (ug/mL) Standard Deviation 122.314	—	—
DLBCL: Plasma Trough Concentrations of Rituximab Cycle 8 Predose	117.61 micrograms per millilitre (ug/mL) Standard Deviation 89.394	—	—

SECONDARY outcome

Timeframe: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1

Population: PK evaluable population. AUC was not estimable for available PK concentrations in DLBCL participants.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=36 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
DLBCL: Area Under the Plasma Concentration-Time Curve (AUC) of Rituximab	NA mcg*hr/mL Standard Deviation NA AUC was not estimable for available PK concentrations in DLBCL participants	—	—

SECONDARY outcome

Timeframe: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1

Population: PK evaluable population. Cmax was not estimable for available PK concentrations in DLBCL participants.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=36 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
DLBCL: Maximum Plasma Concentration (Cmax) of Rituximab	NA micrograms per millilitre (ug/mL) Standard Deviation NA Cmax was not estimable for available PK concentrations in DLBCL participants.	—	—

SECONDARY outcome

Timeframe: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1

Population: PK evaluable population. CL/F was not estimable for available PK concentrations in DLBCL participants.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=36 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
DLBCL: Apparent Total Clearance (CL/F) of Rituximab	NA liter per hour (L/h) Standard Deviation NA CL/F was not estimable for available PK concentrations in DLBCL participants.	—	—

SECONDARY outcome

Timeframe: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1

Population: DLBCL participants with Complete Response/Complete Response Unconfirmed (CR/CRu). The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=28 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 2 Predose	53.97 micrograms per millilitre (ug/mL) Standard Deviation 56.169	—	—
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 3 Predose	101.79 micrograms per millilitre (ug/mL) Standard Deviation 101.223	—	—
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 4 Predose	110.50 micrograms per millilitre (ug/mL) Standard Deviation 101.116	—	—
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 5 Predose	121.67 micrograms per millilitre (ug/mL) Standard Deviation 45.092	—	—
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Baseline	109.40 micrograms per millilitre (ug/mL) Standard Deviation 125.603	—	—
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 7 Predose	157.93 micrograms per millilitre (ug/mL) Standard Deviation 131.178	—	—
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) Cycle 8 Predose	132.57 micrograms per millilitre (ug/mL) Standard Deviation 95.447	—	—

SECONDARY outcome

Timeframe: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1

Population: The overall geometric LS mean plasma trough concentrations of rituximab in participants with DLBCL in the PK population. The number analyzed includes participants who were evaluable at each timepoint.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=36 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
DLBCL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab	70.50 micrograms per millilitre (ug/mL) Interval 57.6 to 86.28	—	—

SECONDARY outcome

Timeframe: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1

Population: DLBCL: R-CHOP 21 or R-CHOP-14; The number analyzed includes participants who were evaluable at each timepoint.

Plasma concentrations of rituximab in participants with DLBCL by chemotherapy regimen cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 14 days (R-CHOP-14) or cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 21 days (R-CHOP-21) in the PK) population.DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=4 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=31 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Cycle 7 Day 7	71.55 micrograms per millilitre (ug/mL) Standard Deviation 26.092	398.76 micrograms per millilitre (ug/mL) Standard Deviation 517.974	—
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Cycle 2 Predose	170.00 micrograms per millilitre (ug/mL) Standard Deviation NA Standard deviation could not be calculated from data for a single participant.	28.37 micrograms per millilitre (ug/mL) Standard Deviation 22.695	—
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Cycle 3 Predose	—	88.92 micrograms per millilitre (ug/mL) Standard Deviation 92.790	—
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Cycle 4 Predose	—	110.50 micrograms per millilitre (ug/mL) Standard Deviation 101.116	—
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Cycle 5 Predose	125.00 micrograms per millilitre (ug/mL) Standard Deviation NA Standard deviation could not be calculated from data for a single participant.	94.00 micrograms per millilitre (ug/mL) Standard Deviation 48.806	—
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Baseline	214.25 micrograms per millilitre (ug/mL) Standard Deviation 233.493	74.25 micrograms per millilitre (ug/mL) Standard Deviation 77.064	—
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Cycle 7 Predose	93.50 micrograms per millilitre (ug/mL) Standard Deviation 79.903	150.13 micrograms per millilitre (ug/mL) Standard Deviation 126.221	—
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Cycle 7 Day 14	42.00 micrograms per millilitre (ug/mL) Standard Deviation NA Standard deviation could not be calculated from data for a single participant.	272.50 micrograms per millilitre (ug/mL) Standard Deviation 103.722	—
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 Cycle 8 Predose	78.50 micrograms per millilitre (ug/mL) Standard Deviation 14.849	123.76 micrograms per millilitre (ug/mL) Standard Deviation 92.606	—

SECONDARY outcome

Timeframe: DLBCL: Cycle (C) 2, C3, C4, C5, C6, End of C8; FL: Induction: C3, C4, C5, C6, C8, Maintenance: C2, C3, C4, C5, C6, C7, C8, C10, C12, End of treatment (4-8 weeks after last dose)

Population: Safety population included all enrolled patients who received at least one dose of study medication.

Patient-assessed satisfaction was evaluated using RASQ. Participants were asked questions regarding convenience and satisfaction for rituximab SC. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants. DLBCL participants could be enrolled at cycle 2, cycle 3, or cycle 4. FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must be able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Each Cycle is 21 days for DLBCL. Each Cycle 21 days during the Induction phase and 2 months during Maintenance phase for FL.

Outcome measures

Outcome measures
Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 Participants Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 Participants Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.	Subcutaneous (SC) Rituximab Participants with CD20+ diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin's follicular lymphoma (FL), who received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 3 Induction	—	81.8 Units on a Scale Standard Deviation 8.66	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 4 Induction	—	76.5 Units on a Scale Standard Deviation 6.26	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 5 Induction	—	79.6 Units on a Scale Standard Deviation 10.30	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 6 Induction	—	95.8 Units on a Scale Standard Deviation 5.89	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 8 Induction	—	83.1 Units on a Scale Standard Deviation 9.18	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 2 Treatment	75.0 Units on a Scale Standard Deviation NA The standard deviation could not be calculated from the data of a single participant.	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 3 Treatment	81.9 Units on a Scale Standard Deviation 10.28	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 4 Treatment	82.1 Units on a Scale Standard Deviation 12.17	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 5 Treatment	83.3 Units on a Scale Standard Deviation 9.96	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 6 Treatment	80.8 Units on a Scale Standard Deviation 9.85	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 8 Treatment	83.8 Units on a Scale Standard Deviation 11.60	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 2 Maintenance	—	83.6 Units on a Scale Standard Deviation 8.71	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 3 Maintenance	—	87.5 Units on a Scale Standard Deviation 19.54	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 4 Maintenance	—	100.0 Units on a Scale Standard Deviation 0.00	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 5 Maintenance	—	80.2 Units on a Scale Standard Deviation 12.55	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 6 Maintenance	—	83.3 Units on a Scale Standard Deviation 16.67	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 7 Maintenance	—	82.7 Units on a Scale Standard Deviation 12.59	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 8 Maintenance	—	93.8 Units on a Scale Standard Deviation 12.50	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 10 Maintenance	—	91.7 Units on a Scale Standard Deviation NA The standard deviation could not be calculated from the data of a single participant.	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain Cycle 12 Maintenance	—	86.3 Units on a Scale Standard Deviation 12.69	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Convenience domain End of Treatment	—	75.0 Units on a Scale Standard Deviation 16.67	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 3 Induction	—	89.4 Units on a Scale Standard Deviation 10.23	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 4 Induction	—	84.1 Units on a Scale Standard Deviation 13.80	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 5 Induction	—	91.7 Units on a Scale Standard Deviation 8.84	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 6 Induction	—	93.8 Units on a Scale Standard Deviation 8.84	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 8 Induction	—	91.3 Units on a Scale Standard Deviation 9.47	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 2 Treatment	87.5 Units on a Scale Standard Deviation NA The standard deviation could not be calculated from the data of a single participant.	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 3 Treatment	83.3 Units on a Scale Standard Deviation 11.53	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 4 Treatment	85.6 Units on a Scale Standard Deviation 13.62	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 5 Treatment	83.3 Units on a Scale Standard Deviation 8.84	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 6 Treatment	84.6 Units on a Scale Standard Deviation 14.57	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 8 Treatment	91.2 Units on a Scale Standard Deviation 12.76	—	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 2 Maintenance	—	92.0 Units on a Scale Standard Deviation 9.28	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 3 Maintenance	—	79.2 Units on a Scale Standard Deviation 20.41	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 4 Maintenance	—	100.0 Units on a Scale Standard Deviation NA The standard deviation could not be calculated from the data of a single participant.	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 5 Maintenance	—	79.7 Units on a Scale Standard Deviation 16.28	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 6 Maintenance	—	87.5 Units on a Scale Standard Deviation 17.68	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 7 Maintenance	—	94.2 Units on a Scale Standard Deviation 9.00	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 8 Maintenance	—	93.8 Units on a Scale Standard Deviation 7.22	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 10 Maintenance	—	50.0 Units on a Scale Standard Deviation NA The standard deviation could not be calculated from the data of a single participant.	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain Cycle 12 Maintenance	—	91.0 Units on a Scale Standard Deviation 13.21	—
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores Satisfaction domain End of Treatment	—	75.0 Units on a Scale Standard Deviation 21.65	—

Adverse Events

Diffuse Large B-Cell Lymphoma (DLBCL)

Serious events: 26 serious events

Other events: 50 other events

Deaths: 14 deaths

Follicular Lymphoma (FL)

Serious events: 23 serious events

Other events: 56 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Diffuse Large B-Cell Lymphoma (DLBCL) n=72 participants at risk Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maxium of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice.	Follicular Lymphoma (FL) n=86 participants at risk Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice.
Blood and lymphatic system disorders Neutropenia	29.2% 21/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	23.3% 20/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Blood and lymphatic system disorders Anaemia	15.3% 11/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	7.0% 6/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Blood and lymphatic system disorders Leukopenia	2.8% 2/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	8.1% 7/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Blood and lymphatic system disorders Thrombocytopenia	5.6% 4/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	3.5% 3/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Blood and lymphatic system disorders Lymphopenia	1.4% 1/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	5.8% 5/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Gastrointestinal disorders Diarrhoea	9.7% 7/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	8.1% 7/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
General disorders Pyrexia	15.3% 11/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	17.4% 15/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Infections and infestations Bronchitis	1.4% 1/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	5.8% 5/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Infections and infestations Herpes Zoster	0.00% 0/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	5.8% 5/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Investigations Neutrophil Count Decreased	12.5% 9/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	1.2% 1/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Musculoskeletal and connective tissue disorders Back Pain	5.6% 4/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	4.7% 4/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Nervous system disorders Paraesthesia	12.5% 9/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	8.1% 7/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Nervous system disorders Headache	4.2% 3/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	8.1% 7/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Respiratory, thoracic and mediastinal disorders Cough	8.3% 6/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	17.4% 15/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	6.9% 5/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	0.00% 0/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Skin and subcutaneous tissue disorders Erythema	0.00% 0/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	7.0% 6/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
General disorders Asthenia	19.4% 14/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	3.5% 3/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
General disorders Influenza Like Illness	2.8% 2/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	10.5% 9/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population
Nervous system disorders Dysgeusia	6.9% 5/72 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population	0.00% 0/86 • Baseline up to 54 months Post study start AEs (AEs occurring on the day of or after the first administration of study drug and up to 28 days after the last dose) and is defined as treatment-emergent adverse event (TEAE). All-Cause Mortality is reported for the ITT population