Author: By Laura Cowen, medwireNews reporter
medwireNews: The bispecific monoclonal antibody mosunetuzumab can induce durable responses in people with heavily pretreated advanced relapsed or refractory follicular lymphoma, suggest phase II data presented at the 63rd American Society of Hematology Annual Meeting & Exposition in Atlanta, Georgia, USA.
L Elizabeth Budde, from City of Hope in Duarte, California, USA, explained that mosunetuzumab binds to CD20 on B cells and CD3 on T cells and acts by engaging and redirecting T cells to eliminate malignant B cells.
She said that in the phase I part of the current phase I/II trial, mosunetuzumab showed encouraging efficacy and manageable safety in patients with grade 1–3a relapsed or refractory follicular lymphoma who had received two or more prior lines of therapy including at least one anti-CD20 antibody and at least one alkylating agent.
The phase II expansion of the study included 90 patients (median age 60 years, 61% men) who were given intravenous mosunetuzumab in 21-day cycles with a step-up dosing strategy designed to mitigate cytokine release syndrome (1 mg on cycle 1 day 1; 2 mg on cycle 1 days 8 and 15, and cycle 2 day 1; 60 mg on cycle 1 day 15 and cycle 2 day 1; 30 mg on cycle 3 day 1 onwards).
There was no mandatory hospitalisation during therapy and treatment was discontinued after eight cycles if patients achieved a complete response (CR) or continued for up to 17 cycles among those with a partial response or stable disease.
L Elizabeth Budde reported that participants had received a median three prior lines of therapy (range 2–10) with 68.9% refractory to their most recent therapy, 78.9% refractory to any prior anti-CD20 antibody, and 53.3% double refractory to both prior anti-CD20 antibody and an alkylating agent. More than three-quarters (76.7%) of participants had stage III or IV disease.
After a median 12.9 months in the study, the objective response rate (ORR) was 80%, with 60% of participants achieving a complete response (CR). This CR rate was significantly greater than the historic CR rate of 14% used as a comparator in the study, the presenter said.
The median times to first response and CR were 1.4 and 3.0 months, respectively, and the median duration of response was 22.8 months, with a median progression-free survival of 17.9 months.
L Elizabeth Budde noted that the CR and overall response rates (ORR) were generally consistent across prespecified subgroups, including among the 47 patients who had progressive disease within 24 months of initial therapy (CR=57%, ORR=85%) and in the 48 double-refractory patients (CR=50%, ORR=71%).
She also said that “mosunetuzumab treatment has a very manageable safety profile.”
Indeed, just 2.2% of participants had a treatment-related adverse event (TRAE) that led to discontinuation.
Cytokine release syndrome occurred in 44.4% of participants but was generally low grade, with just one patient experiencing a grade 3 event and one experiencing a grade 4 event, both of which were fully resolved.
L Elizabeth Budde concluded that mosunetuzumab “is the first T-cell-engaging bispecific antibody to demonstrate clinically meaningful outcomes for patients with relapsed or refractory follicular lymphoma in a pivotal phase II setting.”
She added: “Mosunetuzumab monotherapy is potentially a promising off-the-shelf, outpatient therapy.”
Budde LE, Sehn LH, Matasar M, et al. Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study. Abstract 127; 63rd American Society of Hematology Annual Meeting & Exposition; Atlanta, Georgia, USA: 11–14 December 2021.
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