Triplet Therapy for Follicular Lymphoma Associated With Serious Toxicities

January 16, 2018

Treatment of previously untreated follicular lymphoma with atezolizumab combined with obinutuzumab and bendamustine was associated with widespread adverse events and a treatment-related death, according to an interim analysis of a phase Ib/II cohort study.

Treatment of previously untreated follicular lymphoma with atezolizumab checkpoint-inhibition immunotherapy combined with obinutuzumab and bendamustine was associated with widespread adverse events and a treatment-related death, according to an interim analysis of a phase Ib/II cohort study (abstract 481) presented at the 59th American Society of Hematology Annual Meeting and Exposition, held last month in Atlanta.

Toxicity was largely manageable, however, reported lead study author Anas Younes, MD, of the Memorial Sloan Kettering Cancer Center in New York.

Atezolizumab is a fully-humanized, engineered IgG1 monoclonal antibody that targets programmed death ligand 1 (PD-L1). Obinutuzumab is a humanized anti-CD20 monoclonal antibody. Of 42 patients with grade 1, 2, or 3a follicular lymphoma who were enrolled in the study, 40 had not previously received treatment for their disease. Two patients who had experienced relapsed/refractory follicular lymphoma participated only in the study’s safety run-in phase, along with four previously untreated patients, prior to main enrollment. The safety run-in phase involved intensive safety monitoring, Younes said.

The study involved a 6-month induction period and 2-year maintenance period. Induction involved 28-day treatment cycles with infusions of obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1 and day 1 of cycles 2–6), bendamustine (90 mg/m2 on days 1 and 2 of cycles 1–6) and atezolizumab (840 mg on days 1 and 15 of cycles 2–6). Patients achieving partial or complete response then underwent maintenance therapy with obinutuzumab (1000 mg on day 1 of every other month) and atezolizumab (840 mg on days 1 and 2 each month) for up to 24 months. It is too early to say how durable the reported responses will be, Younes cautioned.

The primary study endpoint was PET/CT-assessed response at the end of induction by an independent review committee.

Two patients died during the study. One patient’s death was deemed to have been treatment-unrelated. The other, however, which occurred after the data cutoff date, was caused by atezolizumab-related cardiac arrest following grade 4-probably immune-mediated-myocarditis and bronchiolitis obliterans.

All patients experienced at least one adverse event, prompting bendamustine dose reductions, treatment interruptions, and discontinuations. The most common treatment-related grade 3/4 toxicities were neutropenia and thrombocytopenia. The most frequent treatment-related serious adverse event was atezolizumab-related infusion-related reactions.