Mosunetuzumab Combo Yields Differentiated Safety Profile Vs SOC in LBCL

At the Society of Hematologic Oncology 2025 Annual Meeting, primary results from the phase 3 SUNMO trial (NCT05171647), which evaluated mosunetuzumab-axgb (Lunsumio) in combination with polatuzumab vedotin-piiq (Polivy; M-Pola) vs rituximab (Rituxan) plus gemcitabine and oxaliplatin (R-GemOx) in patients with autologous stem cell transplant-ineligible relapsed/refractory large B-cell lymphoma, were presented.

They demonstrated that the M-Pola regimen was more efficacious, meeting the primary end point with a 59% reduction in the risk of progression or death vs R-GemOx (HR, 0.41; 95% CI, 0.28-0.61; P <.0001). Regarding safety, the trial showed that treatment-related adverse events (TRAEs) of any grade occurred in 93.3% of the M-Pola arm and 89.1% of the R-GemOx arm; grade 3 or 4 TRAEs occurred in 52.6% and 51.6%, respectively.

The AEs with a difference of at least 5% between the treatment arms that were more common with M-Pola included injection site reactions, cytokine release syndrome (CRS), skin exfoliation, and COVID-19.

Notably, any-grade CRS occurred in 25.9% of patients, with 0.7% having CRS of grade 3 and 5.2% having a serious event of CRS. The median duration of CRS was 3 days (range, 1-11).

Adam J. Olszewski, MD, the presenting author of the results and an associate professor of medicine at The Warren Alpert Medical School of Brown University, spoke with CancerNetwork® about these data, emphasizing the differences in the safety profiles of both combinations.

Transcript:

This is a unique regimen that does not involve any traditional cytotoxic chemotherapy. Even though the overall rate of AEs was similar between the 2 arms, there were very different AEs. Patients [who received] M-Pola did not experience the typical AEs of chemotherapy, with a lot of cytopenias, nausea, tiredness, and there were more local injection site reactions from mosunetuzumab, but they were all very low grade and easily manageable. Most importantly, the rate of CRS was quite low with this regimen. It was the lowest among all studied T-cell-engaging therapies, with only 26% of patients having any CRS, and almost all these events being grade 1. As we describe it, 96% of patients receiving this regimen did not have any significant CRS beyond fever that can be easily managed, and the rate of use of these high-intensity resources like tocilizumab [Actemra] or corticosteroids in patients was only 4%.

In general, this regimen has toxicities; the rate of infections was higher than in the R-GemOx arm, partly because of [COVID-19] infections, which obviously are continuing to occur, but the rate of serious infections was similar between the arms. The rate of grade 3/4 infections was similar. The rate of fatal AEs was very low in both arms. This is a regimen that can be delivered [in an outpatient setting], from my perspective and my patients’ perspective, in a very tolerable manner. [There are] certainly fewer annoying daily AEs, including neuropathy, which was expected to occur with blood; there was significantly less in the M-Pola arm than with R-GemOx. This regimen is quite tolerable for older outpatients who, by definition, are not eligible to get curative, more intense therapy.

Reference

Westin J, Zhang H, Kim W, et al. Mosunetuzumab plus polatuzumab vedotin is superior R-GemOx in transplant-ineligible patients with R/R LBCL: primary results of the phase III SUNMO trial. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, TX. Abstract ABCL-1492.