Mosunetuzumab Monotherapy Yields Notable Efficacy, Manageable Safety for R/R DLBCL, Including for Patients With Prior CAR T-Cell Therapy

Results from a Single-Arm Expansion Cohort Phase 1/2 Trial
 

Findings published in Blood Advances indicated that monotherapy with mosunetuzumab, a humanized immunoglobulin G1-based CD20×CD3 bispecific antibody, demonstrated strong efficacy and a manageable safety profile among patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), including those previously treated with chimeric antigen receptor (CAR) T-cell therapy. 

“Less than half of patients with R/R DLBCL will be suitable candidates for [autologous stem cell transplantation] (ASCT), and of those who are eligible, half will relapse after ASCT,” stated Nancy L Bartlett, MD, Washington University School of Medicine, St. Louis, Missouri, and coauthors. The study authors noted a need for therapies with durable remissions and improved safety among this patient population. 

Thus, Dr Barlett et al aimed to assess the efficacy and safety of mosunetuzumab monotherapy among patients with R/R DLBCL, including those with prior CAR T-cell therapy. The primary end point was the complete response rate compared to the historical control. Secondary end points included the complete response rate assessed by investigators, objective response rate, duration of response and complete response, progression-free survival, and overall survival.

In this expansion-cohort study, 88 patients with R/R DLBCL who had received ≥2 prior lines of therapy, including anthracycline and anti-CD20 therapy, were administered mosunetuzumab intravenously. Among these patients, 73.9% had de novo DLBCL and 26.1% had transformed follicular lymphoma. Step-up dosing during the first cycle was employed to mitigate cytokine release syndrome (CRS). 

The overall response rate was 42%, with a complete response rate of 23.9%. The median time to first response was 1.4 months, and the median progression-free survival was 3.2 months. Among the 26 patients who had previously received CAR T-cell therapy, the complete response rate was 12%. Regarding safety, CRS occurred in 26.1% of patients, primarily of grade 1 to 2 severity, and in the first cycle. A total of 4 patients discontinued treatment due to adverse events.

Dr Bartlett et al concluded, “Mosunetuzumab demonstrated notable efficacy and a manageable safety profile in patients with R/R DLBCL, including those previously treated with CAR-Ts.”

“This manageable safety profile makes it appealing for specific patient groups, such as elderly or unfit patients with previously untreated DLBCL, patients who are not candidates for ASCT or CAR-T therapy, or for use in combination with other therapies, such as polatuzumab vedotin or chemotherapy,” they added. 

Source: 

Bartlett NL, Assouline S, Giri P, et al; Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. Published online August 25, 2023. doi:10.1182/bloodadvances.2022009260