Abstract
GREEN (NCT01905943) is a non-randomized, open-label phase IIIb study investigating obinutuzumab alone or plus chemotherapy in chronic lymphocytic leukemia (CLL). We report a preplanned subgroup analysis of 158 previously untreated CLL patients receiving obinutuzumab–bendamustine (G-B). Patients received six 28-day cycles (C) of G-B: obinutuzumab day (D)1/D2 of C1 (25 mg D1/975 mg D2), 1000 mg D8 and D15 of C1, and D1 of C2–6; and bendamustine 70/90 mg/m2 D1 and D2 of C1–6. The primary endpoint was safety/tolerability. Grade ≥3 adverse events (AEs) occurred in 82.3% of patients, including neutropenia (49.4%), thrombocytopenia (12.0%) and febrile neutropenia (10.8%). Serious AEs included neutropenia (12.7%), febrile neutropenia (9.5%) and pneumonia (7.6%). Rates of grade ≥3 infections and infusion-related reactions were 20.3% and 17.1%, respectively. Due to tumor lysis syndrome (TLS; 8.2%), including two associated fatalities (one in another study cohort), additional risk-minimization measures were implemented. Overall response rate was 81.0%. After 32.8 months’ median observation time, 2-year progression-free survival was 81.8%. Minimal residual disease was undetectable in 59.5% (94/158) and 27.8% (44/158) of patients for blood and bone marrow, respectively. Frontline G-B appears to have manageable toxicity with clinical activity in CLL. Careful TLS risk assessment, pretreatment and monitoring is required.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world [1]
We report the subgroup of previously untreated patients receiving G-B assigned to cohort 1 of GREEN (trial fully accrued since 30 March 2016, with follow-up ongoing), who received a modified obinutuzumab dosing regimen to mitigate infusion-related reactions (IRRs): the initial dose was given in two parts on consecutive days (25 mg on day (D) 1 of cycle (C) 1 at an infusion rate of 12.5 mg/h, followed by 975 mg on D2 at an initial rate of 50 mg/h, 1000 mg on D8 and D15 of C1, and D1 of C2–6 as standard)
Our subgroup analysis of a cohort of first-line patients receiving G-B indicates a similar trend in a larger international, multicenter study, and suggests that G-B may have manageable toxicity and promising efficacy in most patients
Summary
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world [1]. The standard firstline treatment for physically fit CLL patients is chemoimmunotherapy with fludarabine–cyclophosphamide– rituximab (R-FC) [2,3,4,5,6]. Many CLL patients are elderly with comorbidities and ineligible for fludarabine-. Haematology Department, University of Opole, Provincial Hospital, Opole, Poland. 14 University Hospital Vall d’Hebron, Barcelona, Spain. Obinutuzumab plus bendamustine in previously untreated patients with CLL: a subgroup analysis of the. Based treatment [7, 8]. New combinations with less toxicity and alternative chemotherapy backbones are needed
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