Patients with high-risk treatment-refractory mantle cell lymphoma (MCL) show significant survival benefits with treatment with mosunetuzumab combined with polatuzumab vedotin (mosun-pola), new research showed.

“Mosun-pola is an effective off-the-shelf regimen for patients with post-BTKi [Bruton tyrosine kinase inhibitor] relapsed/refractory MCL,” said first author Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, in presenting the findings at the Society of Hematologic Oncology (SOHO) 2025 annual meeting.

“We observed high overall response rates and complete responses, which were consistent across high-risk subgroups.”

MCL, an aggressive subtype of non-Hodgkin lymphoma that is typically not detected until late stage, currently has no cure, and while Bruton tyrosine kinase inhibitors have been highly effective in treatment, patients often eventually develop resistance.

Mosunetuzumab, an off-the-shelf bispecific antibody that binds to CD20 as well as cancerous B cells, in combination with polatuzumab vedotin, an antibody-drug conjugate, has shown synergistic properties in preclinical studies, as well as favorable safety and efficacy as a potential chemo-free option in the treatment of patients with B-cell lymphoma. 

To further investigate a fixed-dose approach with the regimen, Wang and his colleagues conducted the current phase 2 study, involving 42 patients with relapsed or refractory (r/r) MCL who had been treated with at least two prior therapies.

The treatment regimen included subcutaneous mosunetuzumab using a step-up dosing of 5 mg on day 1, 45 mg on day 8, and 45 mg on day 15 in cycle 1, followed by 45 mg on day 1 of each subsequent cycle every 3 weeks for 17 cycles.

In addition, patients received intravenous polatuzumab vedotin, 1.8 mg/kg, on day 1 of cycles 1 through 6.

Premedication with corticosteroids was required in cycle 1 and was optional in cycle 2.

The patients had a median age of 68 years, with 91% having Ann Arbor stage III or IV, and nearly half (48%) had simplified MCL International Prognostic Index scores of 6 or higher.

As many as 71% had three or more high-risk features, all had a median of three prior lines of therapy, ranging from 2 to as many as 9, and 26% had received prior chimeric antigen receptor (CAR) T-cell therapy. 

With a median time on the study of 16 months, ranging from 0 to 41 months, the best overall response rate was 88%, and the complete response rate was 79%.

The median time to first response was 3 months, the median progression-free survival was 19 months, and the overall survival was 21 months.

Importantly, there were no significant differences in response rates among the different high-risk subgroups including those aged 70 years or older (83% of patients), those with prior CAR T-cell therapy (91%), or those with tumor protein p53-mutated (100%).

In terms of safety, the most common treatment-related adverse events were injection site reaction, occurring in 57% of patients, fatigue (50%), cytokine release syndrome (CRS; 43%), and decreased neutrophil counts (33%). 

Of the 18 patients who did develop CRS, all were low-grade (43%; grade 1), and all cases resolved within the first cycle.

There were five grade 5 adverse events, including one case of pneumonia, one of West Nile encephalitis, and three patients who developed COVID-19 pneumonia. 

One patient developed grade 2 immune effector cell-associated neurotoxicity syndrome. 

Wang underscored that the 88% response rate “is a very high response rate for such a heavily treated, sick population.”

The findings underscore that “mosun-pola is a well-tolerated outpatient regimen, with CRS events that were all low grade and resolved within cycle 1,” he added.

“In my opinion, mosun-pola is going to be a very good off-the-shelf option for relapsed refractory mantle cell lymphoma before or after CAR T-cell therapy,” Wang said. 

He clarified that “usually, we would not use it before CAR T-cell therapy” out of concern for effects on the immune system, “but if we had a very sick patient who does not have other options and is not eligible for CAR T-cell therapy, I would definitely use this combination,” Wang noted.

Mosun-Pola Also Significantly Improved Survival vs Chemo in Relapsed Large B-Cell Lymphoma

The novel mosun-pola combination has also shown significant benefits in the treatment of r/r large B-cell lymphoma (r/r LBCL), with the phase 3 SUNMO trial showing a 59% reduction in the risk for disease progression or death compared with standard chemotherapy rituximab-gemcitabine-oxaliplatin.

The study, presented during the session and, as reported by Medscape Medical News, previously presented at the International Conference on Malignant Lymphoma meeting held in June in Switzerland, represents “the first positive phase 3 trial without conventional chemotherapy,” said first author Jason Westin, MD, also of the MD Anderson Cancer Center, in presenting the findings in the SOHO session.

Westin also underscored the combination’s favorable safety profile in the SUNMO population of patients with transplant-ineligible r/r LBCL, particularly regarding the low CRS severity.

“Mosun-pola has the lowest CRS incidence and severity among T-cell directed therapies to date,” he said.

“With 96% of patients not having significant CRS [in the SUNMO trial], mosun-pola may expand patient access to a highly effective therapy and allow for broad outpatient usage at more treatment centers.”

The studies were each sponsored by F. Hoffman-La Roche Ltd.