In a phase Ib/II trial reported in the Journal of Clinical Oncology, Hutchings et al found that the combination of glofitamab and polatuzumab vedotin was associated with high activity in patients with relapsed or refractory large B-cell lymphoma, including high-grade B-cell lymphoma.
Study Details
In the trial, 129 patients were enrolled between November 2019 and September 2024 from sites in Denmark, Israel, Italy, Spain, and the United States. Patients received: obinutuzumab at 1,000 mg in cycle 1/day 1; polatuzumab vedotin at 1.8 mg/kg in cycle 1/day 2 and day 1 of cycles 2 to 6 in 21-day cycles; and glofitamab at step-up doses of 2.5 mg in cycle 1/day 8 and 10 mg in cycle 1/day 15, followed by 30 mg on day 1 of cycles 2 to 12 in 21-day cycles. A total of 44 patients (34.1%) had high-grade B-cell lymphoma. Patients had received a median of two (range = one to seven) previous lines of treatment, including chimeric antigen receptor (CAR) T-cell therapy in 28 (21.7%).
Key Findings
On independent review committee assessment, objective response was observed in 78.3% of all patients, with complete response in 59.7%. Median duration of response was 26.4 months; among patients with complete response, median duration of complete response was 37.8 months.
In patients with high-grade B-cell lymphoma, objective response was observed in 79.5%, with complete response in 65.9%. In patients with prior CAR T-cell therapy, objective response was observed in 75.0%, with complete response in 50.0%.
After a median follow-up of 27.0 months, median progression-free survival was 12.3 months (95% confidence interval [CI] = 8.8–27.7 months). After a median follow-up of 32.7 months, median overall survival was 33.8 months (95% CI = 20.6 months to not evaluable).
Grade 3 or 4 adverse events occurred in 58.9% of patients, most commonly neutropenia (32.6%), COVID-19–related events (9.4%), anemia (8.5%), and thrombocytopenia (8.5%). Serious adverse events were reported in 61.2% of patients. Adverse events led to discontinuation of treatment in 14.7%. Cytokine-release syndrome of any grade occurred in 44.4%, with all events being grade 1 or 2, except for one grade 5 event. Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in four patients (3.1%), all grade 1 or 2.
The investigators concluded: “[Glofitamab plus polatuzumab vedotin] demonstrated high efficacy and durable responses, with manageable safety, in heavily pretreated patients with [relapsed or refractory large B-cell lymphoma], including patients with [high-grade B-cell lymphoma] and previous CAR T-cell therapy failure.”
Martin Hutchings, MD, PhD, of Rigshospitalet and University of Copenhagen, Copenhagen, Denmark, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by F. Hoffmann–La Roche Ltd. For full disclosures of all study authors, visit ascopubs.org.
