Investigational Obinutuzumab 'Safe' with Chemotherapy for CLL
NEW ORLEANS—Patients with chronic lymphocytic leukemia (CLL) can be safely treated with obinutuzumab (GA101, an investigational glycoengineered, type II anti-CD20 monoclonal antibody) in addition to chemotherapy, according to research presented at the 55th American Society of Hematology Annual Meeting and Exposition.
“GA101 plus chemotherapy can be administered safely to patients requiring initial therapy for CLL,” reported Jennifer R. Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, MA, and coauthors. “Our data show GA101 plus FC [fludarabine/cyclophosphamide] or B [bendamustine] has clinical activity in the initial therapy of patients with CLL, warranting further clinical study.”
A total of 41 patients with untreated CLL and performance status 2 or lower were enrolled in this safety, tolerability, and efficacy trial. Patients were treated with GA101 1,000 mg (100 mg intravenous [IV] day 1, 900 mg day 2, 1,000 mg day 8, 1,000 day 15, of cycle 1; 1,000 mg day 1 in cycles 2-8) with either FC (G-FC [GA101-FC] arm: 25/250 mg/m2 IV on days 2-4 of cycle 1, then days 1-3 of cycles 2-6) or B (G-B arm: 70 mg/m2 IV on days 2-3 of cycle 1, then days 1-2 of cycles 2-6).
For the G-FC arm, the overall response rate was 62% (two complete remissions [CRs], three CRi [CR with incomplete blood count recovery], and eight PR). For the G-B arm, overall response was 90% (four CR, five CRi, nine PR).
At a median follow-up of 11.9 months, the most common adverse events (AEs; any grade) for the G-FC arm were infusion-related reactions (IRRs, 91%), nausea (76%), fatigue (57%), constipation (48%), and neutropenia (43%), the authors reported. AEs for the G-B arm included GA101 IRRs (90%), nausea (65%), neutropenia (55%), diarrhea (50%) and pyrexia (45%).
Grade 3/4 GA101 IRRs were associated only with the first administered dose in both study arms.
Serious AEs occurred in 14 participants (six G-FC arm participants and eight G-B arm patients), and included febrile neutropenia (five patients), infections (four patients), IRRs (three patients), nausea (two patients), vomiting (two patients), pyrexia (two patients), and diarrhea, fatigue, tachycardia, tumor lysis syndrome, syncope, mental status change, neutropenia, face swelling and hypertension (one patient each).
In nine patients (seven in the G-FC arm and two in the G-B arm), serious AEs such as grade 3/4 neutropenia, grade 3 thrombocytopenia, and grade 4 pancytopenia led to treatment discontinuation.
“IRRs were the most common AE, but typically occurred during the initial infusions of GA101 and were not dose-limiting,” the coauthors noted. AE rates for patients treated with G-FC or G-B “did not appear to be greater than those in patients treated with standard chemoimmunotherapy.”