How Effective, Safe is Mosunetuzumab/Polatuzumab Vedotin in Pretreated MCL?

Results from a phase 2 trial (NCT03671018) that evaluated mosunetuzumab-axgb (Lunsumio) plus polatuzumab vedotin-piiq (Polivy) showed that, in all patients (n = 42), the overall response rate (ORR) was 88%, with complete responses (CRs) in 79% of patients and partial responses in 9%.

Notably, the ORR was 83% in patients at least 70 years old (n = 18), 91% in patients who received prior CAR T-cell therapy (n = 11), 93% in those with a Ki-67 index score of at least 50%, and 94% in those with pleomorphic/blastoid MCL.

The median progression-free survival and overall survival were 18.6 months (95% CI, 13.9-not estimable [NE]) and 20.7 months (95% CI, 17.0-NE), respectively.

Regarding safety, grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 41% of patients. Any-grade cytokine release syndrome (CRS) occurred in 43% of patients, with no grade 3 or higher events; the median CRS duration and time to first CRS onset relative to last dose were 3 days (range, 1-9) and 2 days (range, 1-5), respectively.

These data were most recently shared at the Society of Hematologic Oncology 2025 Annual Meeting by Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, who spoke with CancerNetwork® about the most prominent takeaways from the trial.

Transcript:

What were the primary findings with this treatment combination?

The primary objective was the ORR. The ORR in this population was 88%, [which is] probably a record in this population. The CR rate in this very hard-to-treat lymphoma [population] was 79%. This is tremendous, and this is a breakthrough in this very sick population. Not only was the ORR high at 88% [and] the CR rate was high at 79%, but across all the bad risk factors, the response rate was the same. That included older [patients], [patients with the] blastoid and pleomorphic subtype, and [those with] a Ki-67 [index score] over 50%. Most importantly, in the 13 patients with the TP53 mutation and deletion, the response rate was 100%. This is a very potent regimen.

Was there anything unexpected in the safety profile of this combination?

The safety [profile] was very light. Mosunetuzumab is a bispecific antibody; it can cause CRS or immune-effector cell-associated neurotoxicity syndrome [ICANS]. The CRS [occurred in] 43% of patients as grade 1 or 2, and there were no grade 3, 4, or 5 CRS toxicities. All the CRS [events] were resolved within the first cycle. The neurotoxicity, which is also indicative of the bispecific antibody therapy, was also very rare, with only 1 [patient] with a grade 1 or 2 [event]; there were no grade 3 neurotoxicities.

There were 5 patients who died from infection after the combination was given, including 3 [cases of COVID-19] and pneumonia; this trial was done during the [COVID-19] pandemic. One [patient died of] pneumonia, and another died from West Nile virus, which is very rare. In this population that had received a median of 3 prior therapies plus our therapy, this was a cause of profound immune compromise, therefore giving rise to the infection rate.

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.