A Study of Obinutuzumab + Bendamustine (BG) in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL)

The CR rate was defined as CR or CR with incomplete blood count recovery (CRi), assessed by the investigator according to iwCLL NCI-WG criteria. The definition of confirmed CR required all of the following criteria as assessed at least 2 months after completion of therapy: peripheral blood lymphocytes < 4 times 10^9 cells/L; absence of significant lymphadenopathy, hepatomegaly, or splenomegaly due to CLL involvement; absence of constitutional symptoms; normal complete blood count (CBC) without need for transfusion or exogenous growth factors, as exhibited by neutrophils >/= 1.5 times 10^9 cells/L, platelets > 100 times 10^9 cells/L, and hemoglobin > 11.0 g/dL; normocellular BM aspirate with < 30% lymphocytes; absence of lymphoid nodules; and BM biopsy without CLL activity. Those fulfilling CR criteria but who have persistent anemia, thrombocytopenia, or neutropenia were considered CRi.

CR is defined in the previous outcome measure. The definition of PR required that the following be documented for minimum 2 months: >/= 50% decrease in peripheral blood lymphocytes from Baseline; reduction in lymphadenopathy; >/= 50% reduction in spleen or liver enlargement; and CBC with one of the following without need for transfusion or exogenous growth factors: polymorphonuclear leukocytes >/= 1.5 times 10^9 cells/L, platelets > 100 times 10^9 cells/L or >/= 50% improvement from Baseline, or hemoglobin > 11.0 g/dL or >/= 50% improvement from Baseline.

Duration of response was defined as the time from the first assessment of CR, CRi, PR, or nodular partial response (nPR) to the first documentation of PD or death, whichever occurred first. CR, CRi, and PR are identified in previous outcome measures. Participants with lymphoid nodules who otherwise met CR criteria were considered nPR. Participants with post-baseline response assessments (excluding progressive disease) but with no end-of-induction treatment response available were censored on Day 1, and those with end-of-induction treatment response available but who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.

PFS was defined as the time from the start of induction treatment (Day 1) to the first occurrence of disease progression, relapse as determined by the investigator using iwCLL NCI WG guidelines, or death (within 28 days after the last dose of study drug), whichever occurred first. Disease progression: at least one of the following: lymphadenopathy; increase in the liver or spleen size by 50% or more or the appearance of hepatomegaly or splenomegaly; an increase in the number of blood lymphocytes by 50% or more with at least 5000 B lymphocytes per microliter; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL. Relapse: Having achieved CR or PR, but after a period of 6 or more months, having demonstrated evidence of disease progression. Participants who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.

OS was defined as the time from the start of induction treatment to death from any cause. Participants who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.

MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in bone marrow aspirate. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture.

MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture.

MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity if the value is <10^-4 (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture. Time to MRD-negative status is defined as the time between MRD positivity (>= 10^-4) or the time of first dose treatment for patients who were missing MRD status assessment at baseline to the first achievement of MRD negativity in the peripheral blood.

MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture. Duration of MRD-negativity among patients who achieved MRD negativity in the study is defined as the period between the first occurrence of MRD-negative status and a subsequent MRD-positive status.

Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state.

Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state.

The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive change from Day 1, Cycle 1 (baseline) indicates improvement. EOT=end of treatment.

The EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) module included assessments of fatigue, treatment side effects, disease symptoms, infection, social activities, and future health worries. Final scores are transformed such that they range from 0 - 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive change from Day 1, Cycle 1 (baseline) indicates improvement. EOT=end of treatment.

An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.

An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.