Fixed-duration glofitamab induces durable complete remissions and demonstrated acceptable safety in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to findings from a phase 2 expansion study presented at the 2022 ASCO Annual Meeting.

A total of 107 patients with DLBCL who received ≥2 prior regimens, including ≥1 anti-CD20 antibody and ≥1 anthracycline, were enrolled in the study and received ≥1 dose of study treatment. Intravenous (IV) glofitamab was administered in step-up doses on day 1 (2.5 mg) and day 8 (10 mg) of cycle 1 and then at the target dose (30 mg) on day 1 of cycles 2 to 12.

The primary end point of the study was complete response (CR) rate by Independent Review Committee (IRC) using Lugano 2014 criteria. Researchers assessed rates of cytokine release syndrome (CRS) using ASTCT criteria.

Of the patients included on the study, the median prior lines of therapies was 3; 59% of patients had received ≥3 prior therapies and 35% had received prior CAR-T therapy. Overall, 85% of patients were refractory to a prior anti-CD20 antibody-containing regimen and to their most recent regimen. In addition, 59% of patients were refractory to their initial therapy and 32% were refractory to prior CAR-T therapy.

After a median follow-up of 9 months, the overall response rate (ORR) was 50% and the CR rate was 35.2%. CR rates were consistent for patients who received prior CAR-T therapy (32%) vs those who did not (37%). The median time to CR was 42 days and 87% of CRs were ongoing at the time of data cutoff.

Of the complete responders, 84% remained in response at 9 months. Of the responders, 61% remained in response at 9 months. The estimated 12-month overall survival was 48% and 92% of complete responders were alive at the time of data cutoff.

“These results are consistent with earlier phase 1 data in 100 pts treated with target glofitamab doses ≥10mg (CR rate: 34%; estimated 20-month CR rate in complete responders: 72%),” wrote Michael Dickinson, MD, Peter McCallum Cancer Centre, Royal Melbourne Hospital, Australia, and colleagues.

CRS occurred in 68% of patients on the study and were mostly grade 1 (51%). Grade 2 CRS occurred in 12% of patients, grade 3 in 3% of patients, and grade 4 in 2% of patients. CRS was most commonly associated with the initial glofitamab dose.

“Fixed-duration glofitamab induces durable complete remissions and has favorable safety in patients with [relapsed/refractory] DLBCL and ≥2 prior therapies, including those with prior exposure to CAR-Ts. Glofitamab is a promising new therapy for pts with heavily pretreated and/or highly refractory DLBCL,” concluded Dr Dickinson and colleagues.

Source:

Dickinson M, Carlo-Stella C, Morschhauser F, et al. Glofitamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and ≥ 2 prior therapies: Pivotal phase II expansion results. Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 7500.