Who Should Receive Mosunetuzumab/Polatuzumab Vedotin as MCL Treatment?

An open-label, randomized phase 2 trial (NCT03671018) evaluated mosunetuzumab-axgb (Lunsumio) plus polatuzumab vedotin-piiq (Polivy) in patients with mantle cell lymphoma. Primary results from that trial were most recently shared at the Society of Hematologic Oncology 2025 Annual Meeting by Michael Wang, MD.

Patients with relapsed/refractory mantle cell lymphoma who had an ECOG performance status from 0 to 2, and who received at least 2 prior therapies—including an anti-CD20 antibody, anthracycline, or bendamustine (Treanda) therapy, and a Bruton’s tyrosine kinase inhibitor—were included.

Mosunetuzumab was administered subcutaneously at 5 mg on day 1 and 45 mg on days 8 and 15 of cycle 1, then 45 mg on day 1 for all subsequent cycles up to cycle 17; polatuzumab vedotin was administered intravenously at 1.8 mg/kg on day 1 of cycles 1 to 6.

The median number of prior therapies was 3 (range, 2-9); additionally, 93% of patients were refractory to their last therapy, 39% had TP53 aberrations, 67% had a Ki-67 index score of 50% or higher, and 48% had a simplified International Prognostic Index for MCL score of at least 6.

Following the presentation, Wang, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, spoke with CancerNetwork® about the dosing schedule and patient population.

Transcript:

How was the dosing for this trial determined?

Mosunetuzumab is a bispecific antibody targeting CD20, with a CD3 [component] to recruit T cells. There are at least 2 other monoclonal antibodies. Epcoritamab-bysp [Epkinly] is subcutaneous, and glofitamab-gxbm [Columvi] is [intravenous]. Mosunetuzumab is the first-ever bispecific antibody developed in lymphoma and approved for lymphoma. Mosunetuzumab is made for [subcutaneous dosing], which is very good for outpatient dosage. Polatuzumab vedotin is an [intravenous infusion] drug, but it is only given for 6 cycles, on the first day of each cycle. After that, because the infusions are short, it can be given in outpatient settings.

What were the characteristics of the patients enrolled on the trial?

There were 44 patients with a median age of 68 years; their median [number of] prior therapies was 3, [and they received] all the way up to 9 cycles—some of the patients received 9 cycles. About 26% received prior CAR T cells, and 93% of people were refractory to the last therapy. This is a very bad risk factor.

Then, patients with TP53 mutations and deletions were 39% of [the population]. TP53 mutations make the tumor very resistant to therapy, and if you do respond with a TP53 mutation, the response duration is short. Next, pleomorphic and blastoid mantle cell lymphoma, which represents a worse morphological prognostic factor, was [seen] in 38% of the patients. [Overall], 71% of patients had 3 or more risk factors. This is very significant. This population typically, to the best of my knowledge, lives for around 6 months and certainly less than a year.

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.