Trial Outcomes & Findings for A Study of Subcutaneous Versus Intravenous MabThera/Rituxan (Rituximab) in Combination With CHOP Chemotherapy in Patients With Previously Untreated CD20-Positive Diffuse Large B-Cell Lymphoma (NCT NCT01649856)

Last Updated: 2017-10-11

Results Overview

Tumor response was assessed per criteria published by Cheson et al (1999). According to consensus recommendations, CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by greater than (\>) 75 percent (%) but still \>1.5 centimeters (cm) in size, and indeterminate bone marrow assessment. The percentage of participants with either response at the end of induction (EOI) was determined with corresponding 95% Pearson-Clopper confidence interval (CI).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

572 participants

Primary outcome timeframe

Up to approximately 4.25 years

Results posted on

2017-10-11

Participant Flow

A total of 662 individuals were screened for entry into the study, and 86 failed the screening procedure. Overall, 576 participants were randomized; 572 received treatment and were included in the analyses.

Participant milestones

Participant milestones
Measure	Rituximab Subcutaneous (SC) Participants with previously untreated, cluster of differentiation (CD) 20-positive diffuse large B-cell lymphoma (DLBCL) received up to 8 cycles of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 milligrams per meter-squared (mg/m\^2) via IV infusion; subsequent doses were given as 1400 milligrams (mg) via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved complete response (CR) or complete response unconfirmed (CRu) after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab Intravenous (IV) Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Overall Study STARTED	369	203
Overall Study COMPLETED	230	125
Overall Study NOT COMPLETED	139	78

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab Subcutaneous (SC) Participants with previously untreated, cluster of differentiation (CD) 20-positive diffuse large B-cell lymphoma (DLBCL) received up to 8 cycles of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 milligrams per meter-squared (mg/m\^2) via IV infusion; subsequent doses were given as 1400 milligrams (mg) via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved complete response (CR) or complete response unconfirmed (CRu) after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab Intravenous (IV) Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Overall Study Withdrawal by Subject	14	14
Overall Study Protocol Violation	4	4
Overall Study Treatment Failure	1	1
Overall Study Death	69	34
Overall Study Stable or Progressed Disease	5	3
Overall Study Lost to Follow-up	20	16
Overall Study Lack of Compliance	6	1
Overall Study Other	20	5

Baseline Characteristics

A Study of Subcutaneous Versus Intravenous MabThera/Rituxan (Rituximab) in Combination With CHOP Chemotherapy in Patients With Previously Untreated CD20-Positive Diffuse Large B-Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab SC n=369 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=203 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Total n=572 Participants Total of all reporting groups
Age, Continuous	60.4 years STANDARD_DEVIATION 13.78 • n=5 Participants	61.0 years STANDARD_DEVIATION 12.63 • n=7 Participants	60.6 years STANDARD_DEVIATION 13.38 • n=5 Participants
Sex: Female, Male Female	165 Participants n=5 Participants	100 Participants n=7 Participants	265 Participants n=5 Participants
Sex: Female, Male Male	204 Participants n=5 Participants	103 Participants n=7 Participants	307 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 4.25 years

Population: Intent-to-Treat (ITT) Population: All participants who completed Baseline and at least one on-treatment efficacy assessment.

Outcome measures

Outcome measures
Measure	Rituximab SC n=342 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=177 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Percentage of Participants With Complete Response (CR) or Complete Response Unconfirmed (CRu)	50.6 percentage of participants Interval 45.2 to 56.0	42.4 percentage of participants Interval 35.0 to 50.0

SECONDARY outcome

Timeframe: At Cycle 7 (each cycle was 14 or 21 days)

Population: ITT Population (CTSQ Subpopulation): All participants who completed the CTSQ at Cycles 3 and 7; number (n) = number of participants in the analysis for the specified domain.

The CTSQ is a validated 16-item questionnaire that measures three domains related to satisfaction with cancer therapy. These include expectations of therapy, feelings about side effects, and satisfaction with therapy. 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.

Outcome measures

Outcome measures
Measure	Rituximab SC n=280 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=141 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Cancer Treatment Satisfaction Questionnaire (CTSQ) Domain Scores Expectations of Therapy (n=280,141)	79.35 units on a scale Standard Deviation 17.422	82.94 units on a scale Standard Deviation 16.536
Cancer Treatment Satisfaction Questionnaire (CTSQ) Domain Scores Feelings about Side Effects (n=276,141)	60.69 units on a scale Standard Deviation 21.594	57.62 units on a scale Standard Deviation 23.339
Cancer Treatment Satisfaction Questionnaire (CTSQ) Domain Scores Satisfaction with Therapy (n=278,141)	85.92 units on a scale Standard Deviation 11.428	83.60 units on a scale Standard Deviation 13.451

SECONDARY outcome

Timeframe: At Cycle 7 (each cycle was 14 or 21 days)

Population: ITT Population (RASQ Subpopulation): All participants who completed the RASQ at Cycles 3 and 7; n = number of participants in the analysis for the specified domain.

The RASQ is a 20-item questionnaire that measures five domains related to the impact of treatment administration. These include physical impact, psychological impact, impact on activities of daily living (ADLs), convenience, and satisfaction. 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.

Outcome measures

Outcome measures
Measure	Rituximab SC n=284 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=144 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores Physical Impact (n=278,140)	86.24 units on a scale Standard Deviation 14.012	81.49 units on a scale Standard Deviation 16.848
Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores Psychological Impact (n=277,141)	85.65 units on a scale Standard Deviation 13.920	78.65 units on a scale Standard Deviation 18.233
Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores Impact on ADLs (n=266,140)	83.77 units on a scale Standard Deviation 16.117	57.38 units on a scale Standard Deviation 19.230
Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores Convenience (n=279,143)	82.32 units on a scale Standard Deviation 13.428	60.14 units on a scale Standard Deviation 17.473
Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores Satisfaction (n=282,141)	89.58 units on a scale Standard Deviation 12.051	77.39 units on a scale Standard Deviation 18.232

SECONDARY outcome

Timeframe: Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)

Population: Safety Population; n = number of participants in the analysis for the specified timepoint.

Duration of rituximab administration was defined as the time from start to end of the SC injection or IV infusion. The median duration was reported.

Outcome measures

Outcome measures
Measure	Rituximab SC n=369 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=203 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Median Duration of Rituximab Administration for Each Treatment Cycle Cycle 3 (n=349,177)	0.1 hours Interval 0.1 to 5.5	2.8 hours Interval 1.0 to 21.4
Median Duration of Rituximab Administration for Each Treatment Cycle Cycle 4 (n=346,173)	0.1 hours Interval 0.0 to 2.5	2.7 hours Interval 0.5 to 8.0
Median Duration of Rituximab Administration for Each Treatment Cycle Cycle 5 (n=332,165)	0.1 hours Interval 0.0 to 2.5	2.6 hours Interval 0.1 to 8.1
Median Duration of Rituximab Administration for Each Treatment Cycle Cycle 6 (n=319,162)	0.1 hours Interval 0.0 to 2.5	2.7 hours Interval 0.1 to 20.0
Median Duration of Rituximab Administration for Each Treatment Cycle Cycle 7 (n=304,156)	0.1 hours Interval 0.0 to 23.6	2.7 hours Interval 0.5 to 6.7
Median Duration of Rituximab Administration for Each Treatment Cycle Cycle 8 (n=305,152)	0.1 hours Interval 0.0 to 2.5	2.55 hours Interval 0.1 to 17.9
Median Duration of Rituximab Administration for Each Treatment Cycle Overall (n=368,201)	4.7 hours Interval 0.1 to 28.7	19.00 hours Interval 1.2 to 57.4
Median Duration of Rituximab Administration for Each Treatment Cycle Cycle 2 (n=361,178)	0.1 hours Interval 0.1 to 23.1	3.0 hours Interval 0.5 to 10.0
Median Duration of Rituximab Administration for Each Treatment Cycle Cycle 1 (n=346,190)	4.0 hours Interval 0.1 to 11.0	4.0 hours Interval 1.2 to 10.0

SECONDARY outcome

Timeframe: Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)

Population: Safety Population.

Chair time was defined as the amount of time the participant occupied an infusion chair/bed for a single treatment cycle of rituximab + CHOP chemotherapy. Where the chair time was not documented for a given cycle, it was reported as "Missing".

Outcome measures

Outcome measures
Measure	Rituximab SC n=369 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=203 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Less than 30 minutes (Cycle 1)	0 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 30 minutes to 1 hour (Cycle 1)	0 percentage of participants	0.5 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 1 to 2 hours (Cycle 1)	1.4 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 2 to 4 hours (Cycle 1)	20.6 percentage of participants	17.2 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 4 to 12 hours (Cycle 1)	69.4 percentage of participants	72.4 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle More than 12 hours (Cycle 1)	7.3 percentage of participants	7.9 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Missing (Cycle 1)	1.4 percentage of participants	2.0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Less than 30 minutes (Cycle 2)	7.3 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 30 minutes to 1 hour (Cycle 2)	2.4 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 1 to 2 hours (Cycle 2)	17.1 percentage of participants	1.1 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 2 to 4 hours (Cycle 2)	56.1 percentage of participants	36.2 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 4 to 12 hours (Cycle 2)	12.2 percentage of participants	60.1 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle More than 12 hours (Cycle 2)	0.3 percentage of participants	1.1 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Missing (Cycle 2)	4.6 percentage of participants	1.6 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Less than 30 minutes (Cycle 3)	5.6 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 30 minutes to 1 hour (Cycle 3)	2.0 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 1 to 2 hours (Cycle 3)	22.1 percentage of participants	0.5 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 2 to 4 hours (Cycle 3)	55.9 percentage of participants	38.9 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 4 to 12 hours (Cycle 3)	12.6 percentage of participants	58.4 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle More than 12 hours (Cycle 3)	0.3 percentage of participants	0.5 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Missing (Cycle 3)	1.7 percentage of participants	1.6 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Less than 30 minutes (Cycle 4)	5.1 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 30 minutes to 1 hour (Cycle 4)	2.8 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 1 to 2 hours (Cycle 4)	21.8 percentage of participants	1.1 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 2 to 4 hours (Cycle 4)	55.0 percentage of participants	36.7 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 4 to 12 hours (Cycle 4)	13.9 percentage of participants	60.6 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle More than 12 hours (Cycle 4)	0.3 percentage of participants	0.6 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Missing (Cycle 4)	1.1 percentage of participants	1.1 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Less than 30 minutes (Cycle 5)	5.0 percentage of participants	0.6 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 30 minutes to 1 hour (Cycle 5)	2.4 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 1 to 2 hours (Cycle 5)	25.2 percentage of participants	1.1 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 2 to 4 hours (Cycle 5)	53.4 percentage of participants	40.2 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 4 to 12 hours (Cycle 5)	12.8 percentage of participants	56.3 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle More than 12 hours (Cycle 5)	0 percentage of participants	0.6 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Missing (Cycle 5)	1.2 percentage of participants	1.1 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Less than 30 minutes (Cycle 6)	3.4 percentage of participants	0.6 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 30 minutes to 1 hour (Cycle 6)	3.1 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 1 to 2 hours (Cycle 6)	23.0 percentage of participants	1.8 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 2 to 4 hours (Cycle 6)	56.7 percentage of participants	42.5 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 4 to 12 hours (Cycle 6)	12.3 percentage of participants	53.3 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle More than 12 hours (Cycle 6)	0 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Missing (Cycle 6)	1.5 percentage of participants	1.8 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Less than 30 minutes (Cycle 7)	18.7 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 30 minutes to 1 hour (Cycle 7)	7.0 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 1 to 2 hours (Cycle 7)	26.9 percentage of participants	4.9 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 2 to 4 hours (Cycle 7)	40.2 percentage of participants	48.8 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 4 to 12 hours (Cycle 7)	6.0 percentage of participants	44.4 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle More than 12 hours (Cycle 7)	0 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Missing (Cycle 7)	1.3 percentage of participants	1.9 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Less than 30 minutes (Cycle 8)	20.3 percentage of participants	0.6 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 30 minutes to 1 hour (Cycle 8)	6.4 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 1 to 2 hours (Cycle 8)	29.3 percentage of participants	4.4 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 2 to 4 hours (Cycle 8)	36.7 percentage of participants	50.9 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle 4 to 12 hours (Cycle 8)	5.8 percentage of participants	43.4 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle More than 12 hours (Cycle 8)	0 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle Missing (Cycle 8)	1.6 percentage of participants	0.6 percentage of participants

SECONDARY outcome

Timeframe: Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)

Population: Safety Population.

Hospital time was defined as the amount of time the participant was in the hospital for the course of one cycle of rituximab + CHOP chemotherapy. Where the hospital time was not documented for a given cycle, it was reported as "Missing".

Outcome measures

Outcome measures
Measure	Rituximab SC n=369 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=203 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Less Than 2 hours (Cycle 8)	18.0 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Less than 2 hours (Cycle 1)	0.3 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 2 to 4 hours (Cycle 1)	3.0 percentage of participants	1.5 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 4 to 6 hours (Cycle 1)	19.8 percentage of participants	20.7 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 6 to 12 hours (Cycle 1)	39.0 percentage of participants	43.8 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 12 to 24 hours (Cycle 1)	8.9 percentage of participants	6.9 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle More than 24 hours (Cycle 1)	26.8 percentage of participants	24.1 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Missing (Cycle 1)	2.2 percentage of participants	3.0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Less than 2 hours (Cycle 2)	3.8 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 2 to 4 hours (Cycle 2)	33.1 percentage of participants	10.1 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 4 to 6 hours (Cycle 2)	27.9 percentage of participants	33.5 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 6 to 12 hours (Cycle 2)	16.3 percentage of participants	38.8 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 12 to 24 hours (Cycle 2)	3.8 percentage of participants	1.1 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle More than 24 hours (Cycle 2)	10.3 percentage of participants	11.7 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Missing (Cycle 2)	4.9 percentage of participants	4.8 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Less Than 2 hours (Cycle 3)	3.6 percentage of participants	0.5 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 2 to 4 hours (Cycle 3)	37.2 percentage of participants	11.9 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 4 to 6 hours (Cycle 3)	30.2 percentage of participants	30.8 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 6 to 12 hours (Cycle 3)	14.5 percentage of participants	41.6 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 12 to 24 hours (Cycle 3)	2.8 percentage of participants	2.2 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle More than 24 hours (Cycle 3)	9.8 percentage of participants	10.3 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Missing (Cycle 3)	2.0 percentage of participants	2.7 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Less Than 2 hours (Cycle 4)	4.5 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 2 to 4 hours (Cycle 4)	36.3 percentage of participants	10.0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 4 to 6 hours (Cycle 4)	27.5 percentage of participants	31.1 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 6 to 12 hours (Cycle 4)	17.6 percentage of participants	42.2 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 12 to 24 hours (Cycle 4)	2.0 percentage of participants	2.8 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle More than 24 hours (Cycle 4)	10.2 percentage of participants	10.6 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Missing (Cycle 4)	2.0 percentage of participants	3.3 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Less Than 2 hours (Cycle 5)	5.0 percentage of participants	0.6 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 2 to 4 hours (Cycle 5)	39.5 percentage of participants	11.5 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 4 to 6 hours (Cycle 5)	26.4 percentage of participants	34.5 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 6 to 12 hours (Cycle 5)	16.0 percentage of participants	37.4 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 12 to 24 hours (Cycle 5)	2.1 percentage of participants	1.7 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle More than 24 hours (Cycle 5)	8.9 percentage of participants	10.9 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Missing (Cycle 5)	2.1 percentage of participants	3.4 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Less Than 2 hours (Cycle 6)	4.3 percentage of participants	0.6 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 2 to 4 hours (Cycle 6)	39.6 percentage of participants	12.6 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 4 to 6 hours (Cycle 6)	26.4 percentage of participants	34.1 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 6 to 12 hours (Cycle 6)	16.3 percentage of participants	38.3 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 12 to 24 hours (Cycle 6)	2.5 percentage of participants	2.4 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle More than 24 hours (Cycle 6)	8.6 percentage of participants	9.0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Missing (Cycle 6)	2.5 percentage of participants	3.0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Less Than 2 hours (Cycle 7)	17.7 percentage of participants	0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 2 to 4 hours (Cycle 7)	40.8 percentage of participants	23.5 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 4 to 6 hours (Cycle 7)	19.9 percentage of participants	36.4 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 6 to 12 hours (Cycle 7)	10.4 percentage of participants	30.9 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 12 to 24 hours (Cycle 7)	2.8 percentage of participants	2.5 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle More than 24 hours (Cycle 7)	5.7 percentage of participants	3.7 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Missing (Cycle 7)	2.5 percentage of participants	3.1 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 2 to 4 hours (Cycle 8)	40.5 percentage of participants	25.8 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 4 to 6 hours (Cycle 8)	21.9 percentage of participants	34.0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 6 to 12 hours (Cycle 8)	8.7 percentage of participants	30.8 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle 12 to 24 hours (Cycle 8)	2.6 percentage of participants	1.3 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle More than 24 hours (Cycle 8)	5.8 percentage of participants	5.0 percentage of participants
Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle Missing (Cycle 8)	2.6 percentage of participants	3.1 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 4.25 years

Population: ITT Population.

EFS events included disease progression, relapse, initiation of other anti-lymphoma therapy, or death. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as greater than or equal to (≥) 50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.

Outcome measures

Outcome measures
Measure	Rituximab SC n=342 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=177 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Number of Participants With an Event-Free Survival (EFS) Event	116 participants	53 participants

SECONDARY outcome

Timeframe: Up to approximately 4.25 years

Population: ITT Population.

EFS was defined as the time from randomization to first occurrence of disease progression, relapse, initiation of other anti-lymphoma therapy, or death, whichever occurred first. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as a ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.

Outcome measures

Outcome measures
Measure	Rituximab SC n=342 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=177 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Duration of EFS	NA months Median EFS was not reached.	NA months Median EFS was not reached.

SECONDARY outcome

Timeframe: Up to approximately 2 years (assessed at Baseline, Day 1 of each cycle [maximum 8 cycles; each cycle was 14 or 21 days], every 3 months thereafter, and/or 4 weeks after early termination)

Population: ITT Population (Responder Subpopulation): All participants who achieved CR or CRu after 4 cycles.

Tumor response was assessed according to criteria published by Cheson et al (1999). Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu. The number of participants who had experienced relapse or death prior to the clinical cut-off date (October 2014) was determined.

Outcome measures

Outcome measures
Measure	Rituximab SC n=178 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=90 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Number of Participants With Relapse or Death at the Time of Primary Analysis	12 participants	5 participants

SECONDARY outcome

Timeframe: Up to approximately 4.25 years

Population: ITT Population (Responder Subpopulation).

DFS was defined as the time from date of initial CR/CRu to the date of relapse or death from any cause. Tumor response was assessed according to criteria published by Cheson et al (1999). Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.

Outcome measures

Outcome measures
Measure	Rituximab SC n=240 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=118 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Duration of Disease-Free Survival (DFS)	NA months Median DFS was not reached.	NA months Median DFS was not reached.

SECONDARY outcome

Timeframe: Up to approximately 4.25 years

Population: ITT Population.

Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.

Outcome measures

Outcome measures
Measure	Rituximab SC n=342 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=177 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Number of Participants With Progression, Relapse, or Death	95 participants	38 participants

SECONDARY outcome

Timeframe: Up to approximately 4.25 years

Population: ITT Population.

PFS was defined as the time from randomization to first occurrence of disease progression, relapse, or death from any cause. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node \>1 cm, following an earlier assessment of CR or CRu.

Outcome measures

Outcome measures
Measure	Rituximab SC n=342 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=177 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Duration of Progression-Free Survival (PFS)	NA months Median PFS was not reached.	NA months Median PFS was not reached.

SECONDARY outcome

Timeframe: Up to approximately 4.25 years

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Rituximab SC n=342 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=177 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Number of Deaths	56 participants	22 participants

SECONDARY outcome

Timeframe: Up to approximately 4.25 years

Population: ITT Population.

OS was defined as the time from randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Rituximab SC n=342 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=177 Participants Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Duration of Overall Survival (OS)	NA months Median OS was not reached.	NA months Median OS was not reached.

Adverse Events

Rituximab SC

Serious events: 155 serious events

Other events: 319 other events

Deaths: 0 deaths

Rituximab IV

Serious events: 77 serious events

Other events: 172 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-LaRoche

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	Rituximab SC n=369 participants at risk Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Rituximab IV n=203 participants at risk Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m\^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Blood and lymphatic system disorders Neutropenia	28.2% 104/369 • Up to approximately 4.25 years Safety Population.	26.6% 54/203 • Up to approximately 4.25 years Safety Population.
Blood and lymphatic system disorders Anaemia	23.8% 88/369 • Up to approximately 4.25 years Safety Population.	19.7% 40/203 • Up to approximately 4.25 years Safety Population.
Gastrointestinal disorders Nausea	21.4% 79/369 • Up to approximately 4.25 years Safety Population.	23.2% 47/203 • Up to approximately 4.25 years Safety Population.
Gastrointestinal disorders Constipation	15.2% 56/369 • Up to approximately 4.25 years Safety Population.	16.7% 34/203 • Up to approximately 4.25 years Safety Population.
Gastrointestinal disorders Diarrhoea	14.1% 52/369 • Up to approximately 4.25 years Safety Population.	9.9% 20/203 • Up to approximately 4.25 years Safety Population.
Gastrointestinal disorders Vomiting	10.8% 40/369 • Up to approximately 4.25 years Safety Population.	8.4% 17/203 • Up to approximately 4.25 years Safety Population.
Gastrointestinal disorders Stomatitis	6.2% 23/369 • Up to approximately 4.25 years Safety Population.	5.4% 11/203 • Up to approximately 4.25 years Safety Population.
Gastrointestinal disorders Abdominal pain	6.5% 24/369 • Up to approximately 4.25 years Safety Population.	5.9% 12/203 • Up to approximately 4.25 years Safety Population.
General disorders Fatigue	19.2% 71/369 • Up to approximately 4.25 years Safety Population.	14.3% 29/203 • Up to approximately 4.25 years Safety Population.
General disorders Pyrexia	10.8% 40/369 • Up to approximately 4.25 years Safety Population.	11.3% 23/203 • Up to approximately 4.25 years Safety Population.
General disorders Asthenia	11.4% 42/369 • Up to approximately 4.25 years Safety Population.	11.8% 24/203 • Up to approximately 4.25 years Safety Population.
General disorders Mucosal inflammation	7.9% 29/369 • Up to approximately 4.25 years Safety Population.	7.9% 16/203 • Up to approximately 4.25 years Safety Population.
General disorders Oedema peripheral	7.3% 27/369 • Up to approximately 4.25 years Safety Population.	4.4% 9/203 • Up to approximately 4.25 years Safety Population.
Skin and subcutaneous tissue disorders Alopecia	23.6% 87/369 • Up to approximately 4.25 years Safety Population.	23.6% 48/203 • Up to approximately 4.25 years Safety Population.
Nervous system disorders Neuropathy peripheral	11.9% 44/369 • Up to approximately 4.25 years Safety Population.	11.8% 24/203 • Up to approximately 4.25 years Safety Population.
Nervous system disorders Paraesthesia	8.7% 32/369 • Up to approximately 4.25 years Safety Population.	6.4% 13/203 • Up to approximately 4.25 years Safety Population.
Nervous system disorders Headache	5.7% 21/369 • Up to approximately 4.25 years Safety Population.	7.4% 15/203 • Up to approximately 4.25 years Safety Population.
Investigations Neutrophil count decreased	22.0% 81/369 • Up to approximately 4.25 years Safety Population.	21.2% 43/203 • Up to approximately 4.25 years Safety Population.
Investigations Weight decreased	7.6% 28/369 • Up to approximately 4.25 years Safety Population.	3.9% 8/203 • Up to approximately 4.25 years Safety Population.
Investigations White blood cell count decreased	13.8% 51/369 • Up to approximately 4.25 years Safety Population.	11.3% 23/203 • Up to approximately 4.25 years Safety Population.
Respiratory, thoracic and mediastinal disorders Cough	11.4% 42/369 • Up to approximately 4.25 years Safety Population.	9.4% 19/203 • Up to approximately 4.25 years Safety Population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.0% 22/369 • Up to approximately 4.25 years Safety Population.	3.0% 6/203 • Up to approximately 4.25 years Safety Population.
Metabolism and nutrition disorders Decreased appetite	7.6% 28/369 • Up to approximately 4.25 years Safety Population.	8.9% 18/203 • Up to approximately 4.25 years Safety Population.
Psychiatric disorders Insomnia	6.2% 23/369 • Up to approximately 4.25 years Safety Population.	6.4% 13/203 • Up to approximately 4.25 years Safety Population.
Gastrointestinal disorders Dyspepsia	5.1% 19/369 • Up to approximately 4.25 years Safety Population.	6.9% 14/203 • Up to approximately 4.25 years Safety Population.
Investigations Lymphocyte count decreased	14.4% 53/369 • Up to approximately 4.25 years Safety Population.	9.9% 20/203 • Up to approximately 4.25 years Safety Population.
Investigations Platelet count decreased	5.1% 19/369 • Up to approximately 4.25 years Safety Population.	5.4% 11/203 • Up to approximately 4.25 years Safety Population.
Metabolism and nutrition disorders Hypokalaemia	5.1% 19/369 • Up to approximately 4.25 years Safety Population.	2.5% 5/203 • Up to approximately 4.25 years Safety Population.
Musculoskeletal and connective tissue disorders Back pain	4.9% 18/369 • Up to approximately 4.25 years Safety Population.	5.4% 11/203 • Up to approximately 4.25 years Safety Population.