Mosunetuzumab Induces High Rates of Complete Remission in Relapsed/Refractory Follicular Lymphoma

Fixed-duration mosunetuzumab demonstrated a favorable safety profile in patients with relapsed or refractory follicular lymphoma (FL) and ≥2 prior therapies, as well as induced high rates of complete remission, according to the results of a phase 2 study published in The Lancet Oncology.

“Mosunetuzumab is a CD20 × CD3 T-cell-engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells. In a phase 1 study, mosunetuzumab was well-tolerated and active in patients with relapsed or refractory B-cell lymphoma,” explained Lihua E Budde, MD, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, and colleagues.

This single-arm, multi-center phase 2 study aimed to evaluate the safety and anti-tumor activity of fixed-duration mosunetuzumab in patients with relapsed or refractory FL. The study was conducted at 49 centers throughout Australia, Canada, Germany, South Korea, Spain, United Kingdom, and United States.

Patients in this study had disease that was relapsed or refractory to ≥2 prior lines of therapy, including an anti-CD20 therapy and an alkylating agent. All patients in the study were aged 18 years or older, with histologically confirmed FL, grade 1 to 3a, and an Eastern Cooperative Oncology Group performance status of 0 to 1.

Patients received intravenous mosunetuzumab in 21-day cycles with cycle 1 step-up dosing: 1 mg on cycle 1 day 1, 2 mg on cycle 1 day 8, 60 mg on cycle 1 day 15 and cycle 2 day 1, 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 was independent review committee-assessed complete response rate (as best response) in all enrolled patients; the primary efficacy analysis compared the observed IRC-assessed 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 this study is ongoing.

Between May 2, 2019, and Sept 25, 2020, a total of 90 patients were enrolled in the study. As of the data cutoff date of August 27, 2021, the median follow-up was 18.3 months (Interquartile range [IQR], 13.8 to 23.3). According to independent review committee assessment, a complete response was recorded in 54 patients (60%; 95% confidence interval [CI], 49.1 to 70.2). They found that the observed complete response rate was significantly higher than the historical control complete response rate with copanlisib of 14% (P <.0001), meeting the primary study end point.

As for adverse events, cytokine release syndrome was the most common, occurring in 40 (44%) of 90 patients, and was predominantly grade 1, in 23 (26%) of 90 patients, and grade 2, in 15 (17%) of 90 patients, and primarily confined to cycle 1. The most common grade 3 to 4 adverse events were neutropenia or neutrophil count decreased, in 24 (27%) of 90 patients, hypophosphataemia in 15 (17%), hyperglycemia in 7 (8%), and anemia in 7 (8%). Serious adverse events occurred in 42 (47%) of 90 patients. No treatment-related grade 5 adverse event occurred.

In conclusion, “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 [FL] and two or more previous therapies,” 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. Lancet Onc. 2022;23(8):1055-1065. doi:10.1016/S1470-2045(22)00335-7