Mosunetuzumab Demonstrates Safety, Efficacy in Patients With Relapsed/Refractory Follicular Lymphoma

Mosunetuzumab, a CD20-CD3 T-cell-engaging bispecific monoclonal antibody, demonstrated a favorable safety profile and high rates of complete remission in patients with relapsed/refractory follicular lymphoma who had previously been treated with ≥2 therapies, according to a phase 2 study published in The Lancet Oncology. Previously, wrote Lihua E Budde, City of Hope National Medical Center, Duarte, CA, and colleagues, “mosunetuzumab was well tolerated and active in patients with relapsed or refractory B-cell lymphoma.”

The single-arm, international, multicenter phase 2 study enrolled 90  patients with grade 1 to 3a relapsed or refractory follicular lymphoma who were treated with ≥2 lines of therapy, including an anti-CD20 therapy and an alkylating agent, between May 2, 2019, and Sept 25, 2020. All patients received intravenous mosunetuzumab in 21-day cycles with cycle 1 step-up dosing: 1 mg on Day of Cycle 1; 2 mg on Day 8 of Cycle 1; 60 mg on Day 15 of Cycle 1 and Day 1 of Cycle 2; and 30 mg on Day 1 of Cycle 3 and onwards. Patients with a complete response completed treatment after cycle 8, whereas patients with a partial response or stable disease continued treatment for up to 17 cycles. The primary end point of the study was complete response rate  in all enrolled patients, with the primary efficacy analysis comparing the observed complete response rate with a 14% historical control complete response rate in a similar patient population receiving the pan-class I PI3K inhibitor copanlisib. Safety was assessed in all enrolled patients, and the study is ongoing.

As of the data cutoff date of August 27, 2021, the median follow-up was 18.3 months. According to independent review committee assessment, a complete response was recorded in 54 patients (60% [95% confidence interval [CI], 49.1 to 70.2). The observed complete response rate was significantly higher than the historical control complete response rate with copanlisib of 14% (P < 0.0001).

Cytokine release syndrome, primarily confined to cycle 1, was the most common adverse event, in 44% of all patients, and was predominantly grade 1 (26% grade 1; 17% grade 2). The most common grade 3/4 adverse events were neutropenia or decreased neutrophil count (27%), hypophosphatemia (17%), hyperglycemia (8%), and anemia (8%). Serious adverse events occurred in 47% patients. There were no treatment-related grade 5 adverse events.

"Fixed-duration mosunetuzumab has a favourable safety profile and induces high rates of complete remissions, allowing potential administration as an outpatient regimen, in patients with relapsed or refractory follicular lymphoma and 2 or more previous therapies,” Dr Budde and colleagues concluded.

 Source:

Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. The Lancet Oncol. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7