Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)

Par. with complete remission (CR), nodular partial remission (nPR), and partial remission (PR) on 2 consecutive visits \>=56 days apart were classified as Rs; those with stable disease (SD)/progressive disease (PD) were classified as NRs. Per the NCIWG 1996 guidelines: CR; no lymphadenopathy/hepatomegaly/splenomegaly/constitutional symptoms, normal hematology, normocellular bone marrow sample for age, \<30% lymphocytes (LC), no lymphoid nodule; PR: \>=50% decrease in LC/lymphadenopathy; nPR: persistent bone marrow nodules; PD: new lesion or increase by \>=50% from baseline; SD: no CR, PR, or PD.

Time frame: Start of treatment (Week 0/Visit 2) until Week 52

Population: Full Analysis Set (FAS): all participants who had been exposed to study drug irrespective of their compliance to the planned course of treatment. Some participants were not evaluable (NE) due to participant withdraw, refusal, non-trial drug-related adverse events, and death.

Cmax is defined as the maximum concentration of drug in plasma samples (collected at the end of the infusion). Ctrough is defined as the concentration of drug in plasma samples at the end of a dosing interval (collected directly before next administration). Ctrough before the first infusion represents residual ofatumumab from participation in Study Hx-CD20-406.

Time frame: Visit 2 (Week 0) and Visit 14 (Month 4)

Population: FAS. Data are provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Duration of response is defined as the time from the initial response (first visit at which response is observed) to progression or death. If the participant had progression between scheduled visits, no progression at the end of the trial, treatment discontinuation for undocumented progression, treatment discontinuation for toxicity or other reason, new anti-cancer treatment, and experienced death or progression after two or more missed visits in a row the endpoint was censored.

Time frame: From the time of the initial response until progression or death (average of 14.1 study months)

Population: FAS

Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 12. Percent change was calculated as (Month 12 SPD minus Baseline SPD)/Baseline SPD \* 100.

Time frame: Baseline (Visit 2) and Month 12

Population: FAS. No participants in the 2000 mg Ofatumumab + Other treatment arm were able to contribute to this measure. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 12. Only participants with a baseline value and a post-baseline value at Month 12 were included in the calculation.

Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 24. Percent change was calculated as (Month 24 SPD minus Baseline SPD)/Baseline SPD \* 100.

Time frame: Baseline (Visit 2) and Month 24

Population: FAS. No participants in the 2000 mg Ofatumumab + Other treatment arm were able to contribute to this measure. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 24. Only participants with a baseline value and a post-baseline value at Month 24 were included in the calculation.

Reduction in tumor size was measured as the percent change in the sum of the products of the diameters of the largest abnormal lymph nodes from Baseline to Week 24. Percent change was calculated as (Week 24 SPD minus Baseline SPD)/Baseline SPD \* 100.

Time frame: Baseline (Visit 2) and Month 4

Population: FAS. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 4. Only participants with a baseline value and a post-baseline value at Month 4 were included in the calculation.

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section of this results record.

Time frame: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Population: FAS

The data collected for this analysis are reported in the overall SAEs of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.

Time frame: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Population: FAS

HAHAs are indicators of immunogenicity to ofatumumab. HAHA levels were assessed for each participant at the end of participation in the study (at their last visit). A positive HAHA status indicates a positive enzyme-linked immunosorbent assay (ELISA) result, an inconclusive status indicates a negative ELISA result at ofatumumab concentration above the threshold at which ofatumumab may interfere with the assay, and a negative status indicates a negative ELISA result at ofatumumab concentration below the threshold.

Time frame: Screening and post ofatumumab (up to Study Month 32)

Population: FAS. During the study, samples were to be taken at the last visit; however, this may not have been possible, such as in cases of death, or when the visit was not obvious as the last visit. Therefore, some samples were not available or were not collected.

The data collected for this analysis are reported in the overall Serious Adverse Events (SAEs) of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.

Time frame: From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Population: FAS

OS is defined as the time from allocation to death.

Time frame: Time from start of study treatment (Week 0 of Visit 2) until date of death or time that participant was no longer followed (median of 18.0 months)

Population: FAS

PFS is defined as the time from randomization until progression (prog.)/death. Prog. events are defined by well-documented and verifiable data; other data are censored. If the par. had prog. between scheduled visits, died before the first assessment, or died between adequate visits, the endpoint was considered progressed. If there was no prog. at the end of the trial, treatment discontinuation for undocumented prog./toxicity/other reason, new anti-cancer treatment, and death/prog. after \>=2 missed visits in a row, the endpoint was censored. Clinical prog. is not considered as a prog. endpoint.

Time frame: Start of treatment (Week 0 of Visit 2) until progression or death (average of 14.1 study months)

Population: FAS

Time to next chronic lymphocytic leukemia (CLL) treatment is defined as the time from treatment allocation/randomization (Visit 2) until the time of the first administration of the next CLL treatment other than ofatumumab (or HuMaxCD20, a fully human monoclonal antibody to CD20 that is expressed on the surface of B-cells).

Time frame: Time from start of study treatment (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (average of 14.8 study months)

Population: FAS