Drug Combo Outpaces Standard Chemo in R/R LBCL

Medscape

09-07-2025

A combo of the novel bispecific antibody mosunetuzumab and the antibody-drug conjugate polatuzumab vedotin (Mosun-Pola) significantly outperformed standard chemotherapy in transplant-ineligible patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), an industry-funded phase 3 trial found.
Over a median 23.2 months follow-up, progression-free survival in patients with R/R LBCL was a median of 11.5 months for Mosun-Pola vs 3.8 months for the rituximab-gemcitabine-oxaliplatin (R-GemOx) regimen (hazard ratio [HR], 0.41, P < .0001), reported lead author Jason Westin, MD, MS, professor, Department of Lymphoma & Myeloma, MD Anderson Cancer Center, Houston, at the annual International Conference on Malignant Lymphoma (ICML) meeting in Lugano, Switzerland.
The other primary endpoint, objective response rate, was higher in the Mosun-Pola group than the R-GemOx group (70.3% vs 40.0%; P < .0001).
The data from the SUNMO trial 'demonstrate the potential of Mosun-Pola as a well-tolerated combination that can be delivered in the outpatient setting for a fixed duration and prolong remission for people with R/R LBCL,' said Westin in an interview.
As Westin noted, about 40% of newly diagnosed patients with LBCL don't respond to rituximab-based immunochemotherapy or relapse after treatment. More than half of the patients with R/R LBCL, he said, are not eligible for two second-line treatments — chimeric antigen receptor (CAR) T-cell therapy and high-dose chemotherapy with autologous stem-cell transplantation.
While there are other options, 'many patients lack access to highly effective therapies due to logistical and toxicity-related concerns,' Westin said.
A New Combo Gets Tested
Enter Mosun-Pola, which combines mosunetuzumab (Lunsumio), which is FDA-approved for patients with R/R follicular lymphoma after two or more lines of therapy, and polatuzumab vedotin (Polivy), which is FDA-approved for both newly diagnosed and R/R LBCL with conventional chemotherapy.
'Mosunetuzumab and polatuzumab vedotin have different mechanisms of action,' Westin said. 'By combining these medicines, we hoped to build upon the success of these drugs when used alone and improve outcomes.'
For the study, researchers randomly assigned 138 patients to Mosun-Pola (8 cycles every 21 days) and 70 to R-GemOx (eight cycles every 14 days). Among all patients, 43.8% had received one prior therapy, and 73.6% had primary refractory disease or relapse < 12 months from first-line therapy. The study population had a median age of 62-63 years, and the oldest patient was 87.
The complete response rate was 51.4% for Mosun-Pola and 24.3% for R-GemOx. After 1 year, 72.6% of patients with complete response were still in remission (95% CI, 61.4-83.8) vs 44.1% 95% CI, 13.2-74.9), respectively.
Safety Evaluation Favors Mosun-Pola
Interim overall survival favored Mosun-Pola (median, 18.7 months; 95% CI, 14.1-not evaluable, vs 13.6 months; 95% CI, 9.9-not evaluable, respectively; HR, 0.80; 95% CI, 0.54-1.20).
Among 135 Mosun-Pola- and 64 R-GemOx-treated patients evaluated for safety, rates of grades 3-4 events were similar in the groups (58.5% vs 57.9%, respectively) as were grade 5 events (5.2% vs 6.3%, respectively). Rates of thrombocytopenia (8.9% vs 65.6%, respectively) and peripheral neuropathy (24.4% vs 42.2%, respectively) were much lower in the Mosun-Pola group.
In his presentation at the ICML meeting, Westin said any grade of cytokine release syndrome (CRS) was seen in 25.9% of patients. 'However, grade 2 or above was observed in only 4.4% of patients, and grade 1, which is a fever only, was observed in 21.5% of patients. This means that of the patients treated with Mosun-Pola, 96% did not have any significant CRS.'
No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were seen in the Mosun-Pola group.
Outside Specialist Is Not Wildly Impressed
In an interview, Stephen D. Smith, MD, associate professor at the University of Washington and medical oncologist at the Fred Hutchinson Cancer Center, Seattle, who was not involved in the SUNMO trial, noted that the current treatment landscape is complex.
'This is a crowded field, and the added value of this study is modest,' he said. 'The comparator R-GemOx is a niche regimen — mainly used for bridging to CAR-T or even palliative therapy in the US. Other options are approved in this space, so beating R-GemOx in progression-free survival is only a small part of a complex picture.'
Smith pointed out that several competing therapies already exist in this space. 'We already have FDA approvals for epcoritamab and glofitamab in the third-line space, and these same drugs hold promise — though are not approved — when combined with R-GemOx in second line or later DLBCL treatment,' he said. Two other options are loncastuximab and tafasitamab with lenalidomide, he said.
Still, Mosun-Pola 'Dunked' on R-GemOx
Regarding the study's design, Smith noted that it includes transplant-ineligible patients, which is not the same as CAR T-cell therapy-ineligible. 'CAR T-cell therapies are the main priority for high-risk, early relapsed DLBCL, and for third-line patients.'
Still, he said that Mosun-Pola 'dunked on R-GemOx' in terms of progression-free survival, and 'from anecdotal experience, patients feel reasonably good on these therapies, especially after getting through the first cycle and if they can dodge infections.'
When asked for a response, Westin noted that the positive outcomes in efficacy were achieved with the favorable toxicity profile. The lowest rate of CRS of any T-cell directed therapy to date is an important differentiating factor which could allow usage at more centers than currently use bispecific antibodies.
Also, he said, 'Mosun-Pola does not include conventional chemotherapy, a first for a positive phase 3 trial in this space.'
As for the role of R-GemOx, he said 'this is a commonly accepted treatment in the United States and globally for patients who are not intended for transplant. It's both listed in guidelines worldwide and is the control arm for at least five studies in this space.'
Next Up: Submission to FDA
What now? Genentech plans to submit the study findings to regulatory agencies such as the FDA, and it notes that the National Comprehensive Cancer Network has added Mosun-Pola as a recommendation for the treatment of people with second-line DLBCL who are not headed to transplant.
However, Smith said he doesn't expect the study findings 'will change standard of care, which is rapidly evolving with several options all of which are likely — or proven to be — better than R-GemOx,' Smith said.
As for cost, Westin declined to discuss the potential price of a Mosun-Pola product. Smith said it would be extremely expensive.