Obinutuzumab is a novel, glycoengineered, type II CD20 monoclonal antibody designed to increase direct and antibody-dependent cellular cytotoxicity. Early phase 1/2 studies in patients with chronic lymphocytic leukemia (CLL) demonstrated single-agent activity with treatment-related neutropenia. GALTON is a nonrandomized, parallel group, phase 1b study of the safety and preliminary efficacy of obinutuzumab plus fludarabine and cyclophosphamide (FC) or obinutuzumab plus bendamustine in the initial therapy of patients with CLL.
Patients with untreated CLL who required therapy and who had a good performance status were treated with either obinutuzumab plus FC or obinutuzumab plus bendamustine. Physicians could reduce the doses of FC or bendamustine after the first cycle if tolerance to chemotherapy became a concern. Each cycle was 28 days.
The primary end point was safety of obinutuzumab with chemotherapy. Secondary end points included response rates based on the International Workshop on Chronic Lymphocytic Leukemia criteria, using computed tomography scans to confirm response.
Brown and colleagues enrolled 41 patients with a median follow-up time of 11.9 months. In the obinutuzumab plus FC arm, the most common adverse events (AEs) that occurred in 9 or more patients were obinutuzumab infusion-related reactions ([IRRs]; 91%), nausea (76%), fatigue (57%), constipation (48%), and neutropenia (43%). In the obinutuzumab plus bendamustine arm, the most common AEs were obinutuzumab IRRs (90%), nausea (65%), neutropenia (55%), diarrhea (50%), and pyrexia (45%). In both cohorts, grade 3 to 4 obinutuzumab IRRs only occurred with the first dose. Fourteen patients experienced serious AEs, including febrile neutropenia, infections, IRRs, nausea, vomiting, and pyrexia.
Of the patients evaluable for response, the overall response rate was 62% in the obinutuzumab plus FC arm, and 90% in the obinutuzumab plus bendamustine arm. Overall, 4 patients in the obinutuzumab plus FC arm and none in the obinutuzumab plus bendamistine arm achieved stable disease during and after therapy. In addition, no patient experienced disease progression during the study.
Brown and colleagues concluded that obinutuzumab plus chemotherapy is effective and can be administered safely to patients as initial therapy for CLL. Overall, IRRs were the most common AE, but typically occurred during the initial infusions of obinutuzumab; they were not dose-limiting. The efficacy and tolerability of obinutuzumab plus FC or obinutuzumab plus bendamustine in patients with CLL warrant further clinical study.
References
Brown JR, O'Brien S, Kingsley CD, et al. Safety and efficacy of obinutuzumab (GA101) with fludarabine cyclophosphamide (G-FC) or bendamustine (G-B) in the initial therapy of patients with chronic lymphocytic leukemia (CLL): results from the phase 1b Galton trial (GAO4779g). Blood. 2013;122(21). Abstract 523.
Safety and Efficacy of Obinutuzumab (GA101) with Fludarabine Cyclophosphamide or Bendamustine in the Initial Therapy of Patients with Chronic Lymphocytic Leukemia: Results from the Phase 1b GALTON Trial
Last modified: August 30, 2021