Mosunetuzumab as a Treatment Option for Patients With Relapsed or Refractory Mantle Cell Lymphoma
In a recent phase I/II trial, mosunetuzumab, a bispecific antibody used to treat follicular lymphoma, showed encouraging efficacy and tolerability as a treatment option for patients with relapsed or refractory mantle cell lymphoma (R/R MCL), particularly in those with progressive disease following Bruton tyrosine kinase inhibitor (BTKi) therapy. This study was presented at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, CA.
Mantle cell lymphoma, a rare and challenging form of non-Hodgkin lymphoma, becomes particularly difficult to manage when it relapses or resists treatment. Although BTKi therapy is a common treatment option for MCL, there is still a need for alternative therapies. Mosunetuzumab, a CD20xCD3 bispecific antibody, leverages T-cell redirection to target malignant B cells, including those causing disease. In a study published in early 2024, mosunetuzumab demonstrated durable remissions with an acceptable safety profile in patients with R/R B-cell lymphomas.
In an expansion cohort for mosunetuzumab monotherapy, researchers enrolled 25 patients with R/R MCL who had received at least one prior BTKi-containing regimen. The median age of participants was 70 years (range, 50 to 89), with most presenting advanced-stage disease and refractory characteristics. Mosunetuzumab was administered intravenously at 21-day cycles with a step-up dosing approach during the initial cycle. The treatment duration varied based on patient response, with complete responders discontinuing by cycle 8 and others continuing up to 17 cycles. Investigators evaluated safety, tolerability, and efficacy using established criteria, while monitoring adverse events.
The best overall response rate was 44%, with 24% achieving a complete response (CR). Median progression-free survival was 3.7 months, while the median overall survival reached 7.3 months. Responses were durable in some cases, with CR lasting a median of 18 months. Subgroup analyses indicated consistent efficacy even among patients with high-risk features, such as elevated mantle cell lymphoma prognostic index scores.
Safety data revealed that cytokine release syndrome was the most frequent adverse event (AE; 52%), although this was primarily low-grade and confined to early treatment cycles. Other common side effects included fatigue (36%) and fever (36%). Serious AEs (excluding fatal progressive disease) occurred in 14 patients (56%), with 10 (40%) related to treatment.
The researchers emphasized that mosunetuzumab represents a promising therapeutic option for patients with R/R MCL due to its tolerability, off-the-shelf availability, lack of mandatory hospitalization, and convenient dosing schedule. Currently, mosunetuzumab is being investigated in combination with polatuzumab vedotin for those with R/R MCL (NCT03671018).
“Fixed-duration mosunetuzumab demonstrated encouraging single-agent activity in a challenging-to-treat population of patients with high-risk and refractory MCL,” the researchers concluded.
Reference
Budde LE, Matasar M, Sehn LHH, et al. Mosunetuzumab monotherapy demonstrates encouraging activity and a manageable safety profile in patients with heavily pre-treated relapsed or refractory mantle cell lymphoma. Paper presented at: 66th ASH Annual Meeting & Exposition. San Diego, CA. December 7, 2024. https://ash.confex.com/ash/2024/webprogram/Paper197902.html.