Glofitamab Combination Demonstrates Promising Durability in Relapsed/Refractory Large B-Cell Lymphoma
New data presented reveal a high objective response rate and encouraging durability of response with the combination of glofitamab and polatuzumab vedotin in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL), including high-grade B-cell lymphoma (HGBCL). The phase Ib/II trial results, published October 20, 2025, in J Clin Oncol. (doi:10.1200/JCO-25-00992), offer a potential new treatment option for a patient population with limited therapeutic choices.
LBCL, an aggressive type of non-Hodgkin lymphoma, frequently enough relapses after initial treatment, creating a significant unmet need for effective therapies. The study evaluated glofitamab, a bispecific antibody, in combination with polatuzumab vedotin, an antibody-drug conjugate, administered in 21-day cycles, with glofitamab given for 12 cycles and polatuzumab vedotin for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients were hospitalized for 24 hours following the initial glofitamab dose.
The overall and HGBCL populations had a median age of 67.0 years (range, 23-84) and 66.5 years (range, 24-84), respectively. A majority of patients were male (63.6% vs 63.6%) with an ECOG performance status of 0 or 1 (94.6% vs 93.2%) and Ann arbor stage III/IV disease (76.7% vs 72.7%).IPI scores were distributed as 2 (30.2% vs 29.5%), 3 (24.0% vs 20.5%), and 4 (23.3% vs 25.0%). Notably, 72.9% and 70.5% of the overall and HGBCL groups, respectively, exhibited extranodal involvement at study start, while 29.5% vs 22.7% had bulky disease. A substantial proportion of patients had received prior lines of therapy (58.9% vs 45.5%), with many demonstrating refractoriness to first-line (62.0% vs 70.5%) or any prior therapy (79.1% vs 81.8%).
The trial’s primary endpoint was IRC-assessed objective response rate (ORR) per PET-CT scan using Lugano 2014 criteria. Secondary endpoints included investigator-assessed ORR, duration of response (DOR), duration of complete response (DOCR), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and safety.
Safety data revealed that 99.2% of patients experienced any-grade adverse events (AEs), with the most frequent being cytokine release syndrome (CRS) (43.4%), neutropenia (41.9%), peripheral neuropathy (26.4%), diarrhea (24.0%), COVID-19 infection (23.3%), and pyrexia (20.2%). Grade 3 or 4 AEs occurred in 58.9% of patients, with neutropenia (32.6%), COVID-19 infection or pneumonia (9.4%),anemia (8.5%), thrombocytopenia (8.5%), and tumor flare (7.0%) being the most common. Grade 5 AEs were observed in 9.3% of patients, and serious AEs occurred in 61.2%. AEs led to treatment discontinuation in 14.7% of patients, with 12.4% discontinuing glofitamab and 8.5% discontinuing polatuzumab vedotin. CRS, including grade 3 and 5 events, was observed in 29.4% of patients, with only one instance of grade 3 and grade 5 CRS reported.
The median time to CRS onset following the 30-mg once-daily dose of glofitamab was 36.2 hours (range, 18.5-55.9). Common CRS management strategies included tocilizumab (33.9%), intravenous fluids (23.2%), low-flow oxygen (19.6
