Mosunetuzumab Combo May Save Lives in Mantle Cell Lymphoma

At the Society of Hematologic Oncology 2025 Annual Meeting, Michael Wang, MD, presented primary results from an open-label, randomized phase 2 trial (NCT03671018) that evaluated mosunetuzumab-axgb (Lunsumio) plus polatuzumab vedotin-piiq (Polivy) in patients with mantle cell lymphoma.

The secondary end point of progression-free survival (PFS) was met, with a median PFS of 18.6 months (95% CI, 13.9-not estimable), and a 12-month PFS rate of 74.8% (95% CI, 60.2%-89.4%).

Wang, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, spoke with CancerNetwork® about the rationale and implications of the trial results following the presentation.

He emphasized that with mosunetuzumab attacking the CD20 antigen and polatuzumab vedotin targeting the CD79b antigen, both agents complement each other well; they were shown to be synergistic in preclinical work. The positive nature of the results may also support the possibility to use this combination as a bridge therapy in patients with high-risk factors.

Transcript:

CancerNetwork: Why was this phase 2 study evaluating M-Pola in relapsed/refractory MCL necessary?

Wang: We had 44 patients in this clinical trial, and many patients had high-risk factors. [For example], 71% of patients had 3 or more risk factors. Their [expected] survival is less than a year. But in this very heavily [pretreated] and sick population, we used this combination. Why did we use this combination? Because [with] the combination, mosunetuzumab attacks the CD20 antigen on the surface of a tumor cell, while [polatuzumab vedotin] targets the CD79b antigen on the surface of the cells. We are attacking 2 targets with 2 potent agents. Each agent has generated data in mantle cell lymphoma and large B-cell lymphoma. The combination is complementary to each other, and in preclinical work, it was synergistic.

What are the clinical implications of these study results?

When we have patients who have big tumors, whose tumors are TP53 mutated, [have a] Ki-67 [index score] over 50%, and who have blastoid or pleomorphic [subtype], [or have] all these horrible risk factors, and where chemotherapy, radiation therapy, or other therapies don’t seem to work—especially for those who received prior CAR T-cell therapies and relapsed after—their life expectancy is around 6 months. For that, this combination can rescue people with a median PFS of 18 months. [There’s a life expectancy] of less than 6 months, but median PFS was 18 months, and median OS was 21 months. This is tremendous. This will bridge to other therapies that are upcoming in clinical trials or other standard therapies. This is a lifesaving combination therapy.

Reference

Wang ML, Kamdar M, Assouline S, et al. Fixed-duration outpatient subcutaneous mosunetuzumab + polatuzumab vedotin shows robust efficacy in a phase 2 study of relapsed/refractory (R/R) post-BTK inhibitor mantle cell lymphoma (MCL). Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 2-6, 2025. Houston, TX. Abstract MCL-1493.