In the global phase III SUNMO trial, the combination of a bispecific antibody and an antibody-drug conjugate was compared with rituximab plus gemcitabine and oxaliplatin (GemOx) in the treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL) who were ineligible for autologous stem cell transplant (ASCT). Treatment with mosunetuzumab-axgb (a bispecific engager that targets CD20
× CD3) and polatuzumab vedotin-piiq (an antibody-drug conjugate that targets CD79b protein) met its primary endpoints, with statistically significant and clinically meaningful improvements in both progression-free survival and objective response rate vs rituximab plus GemOx.
Hematologist/oncologist Adam J. Olszewski, MD, Associate Professor of Medicine at The Warren Alpert Medical School of Brown University, Providence, Rhode Island, presented these results of the primary analysis of this trial on behalf of his colleagues at the 2025 Society of Hematologic Oncology (SOHO) Annual Meeting.1 “SUNMO is the first positive phase III trial for treatment of second-line and further diffuse large B-cell lymphoma without conventional cytotoxic chemotherapy,” he said.
Jason Westin, MD, MS, FACP, FASCO
SUNMO study coauthor Jason Westin, MD, MS, FACP, FASCO, Professor of Lymphoma and Director of Lymphoma Clinical Research at The University of Texas MD Anderson Cancer Center, Houston, commented in a press release. “If approved, this off-the-shelf treatment combination of mosunetuzumab and polatuzumab vedotin could be administered over a fixed period of time, without mandatory hospitalization or traditional chemotherapy, which could provide a meaningful option for patients with relapsed or refractory LBCL.”
Study Details
As of February 2025, 208 patients with relapsed or refractory LBCL who were not eligible for ASCT participated in the randomized SUNMO trial. A total of 138 patients received eight subcutaneous cycles of mosunetuzumab plus six intravenous cycles of polatuzumab vedotin (every 21 days), and 70 patients received rituximab plus GemOx intravenously (every 14–21 days).
More than 75% of patients in both treatment arms had diffuse large B-cell lymphoma. Other B-cell lymphomas included transformed follicular lymphoma and high-grade B-cell lymphoma. Overall, nearly half of patients had received one prior therapy, and more than two-thirds of patients had primary refractory disease or early relapse (disease relapse within 12 months of first-line treatment).
The dual primary study endpoints (by independent review committee assessment) were objective response rate and progression-free survival. The key secondary study endpoint was overall survival. By August 2024, 208 patients of the planned 222 patients were enrolled.
Key Results
At a median follow-up of 23.2 months, progression-free survival was significantly improved at 11.5 months (95% confidence interval [CI] = 5.6–17.6 months) with mosunetuzumab plus polatuzumab vedotin vs 3.8 months (95% CI = 2.9–4.1 months) with rituximab plus GemOx (hazard ratio [HR] = 0.41, 95% CI = 0.28–0.61, P < .0001). These results translate to a 59% risk reduction for disease progression or death with the immunotherapy combination vs the chemotherapy.
Based on an exploratory analysis, the progression-free survival benefit of mosunetuzumab plus polatuzumab vedotin was consistent across clinically relevant subgroups. These subgroups included those who had received second-line therapy (HR = 0.38, 95% CI = 0.22–0.67) and those who had primary refractory disease to initial therapy or early relapse (HR = 0.44, 95% CI = 0.29–0.67).
An interim analysis showed that overall survival numerically favored the immunotherapy combination vs the chemotherapy regimen, with a median overall survival of 18.7 vs 13.6 months. These results currently correspond to a hazard ratio of 0.80, “but the formal statistical testing will require further follow-up,” Dr. Olszewski noted.
As for objective response rates, the immunotherapy combination yielded a 70.3% objective response rate, with 51.4% complete responses and 18.8% partial responses. In comparison, the chemotherapy regimen yielded a 40.0% objective response rate, with 24.3% complete responses and 15.7% partial responses.
The median duration of response to the immunotherapy combination has not been reached with the current follow-up of about 2 years. “Nearly 75% of patients with a complete response [to mosunetuzumab plus polatuzumab vedotin] were still in remission at 1 year,” stated Dr. Olszewski.
Toxicity Profile
The adverse event rates were found to be comparable between the two treatment arms. For those who received mosunetuzumab plus polatuzumab vedotin, 93.3% experienced treatment-related serious adverse events, compared with 89.1% of those who received rituximab plus GemOx. Grade 3 or 4 treatment-related adverse events were reported in 52.6% of those given the immunotherapy combination, compared with 51.6% of those given the chemotherapy regimen. According to the study investigators, fewer adverse events leading to treatment discontinuation were observed with the immunotherapy combination.
As expected, there was a different profile for adverse events between the two treatment arms. For example, infections were reported in 51.1% of those given the immunotherapy combination vs 31.3% of those given the chemotherapy regimen. However, the occurrence of peripheral neuropathy was higher in the chemotherapy arm (42.2% vs 24.4%), although no grade ≥ 3 cases were seen in either treatment arm.
As for the incidence of cytokine-release syndrome associated with the combination of mosunetuzumab plus polatuzumab vedotin, Dr. Olszewski noted this complication occurred infrequently (25.9%), with most cases grade 1. The median onset to first occurrence of cytokine-release syndrome was 3 days, and the median duration was 3 days. No immune effector cell–associated neurotoxicity syndrome events were reported.
“Mosunetuzumab plus polatuzumab vedotin had the lowest cytokine-release syndrome incidence and severity among T-cell–directed therapies to date, with 96% of patients not having a significant cytokine-release syndrome beyond fever,” Dr. Olszewski remarked.
DISCLOSURE: The SUNMO trial was sponsored by F. Hoffmann–La Roche Ltd. For full disclosures of study authors, visit sohoonline.org.
REFERENCE
1. Westin J, et al: 2025 SOHO Annual Meeting. Abstract ABCL-1492. Presented September 5, 2025.
EXPERT POINT OF VIEW
Julie Vose, MD, MBA, FASCO, shared these comments on the findings of the phase III SUNMO trial with the immunotherapy combination of mosunetuzumab-axgb plus polatuzumab vedotin-piiq in patients with relapsed or refractory large B-cell lymphoma who were not eligible for autologous stem cell transplantation. Dr. Vose is Chief of the Division of Oncology and Hematology at the University of Nebraska Medical Center/Nebraska Medicine, Fred & Pamela Buffett Cancer Center, Omaha; and a member of the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) panel for B-cell lymphomas.
Julie Vose, MD, MBA, FASCO
“The phase III SUNMO Trial compared mosunetuzumab (a bispecific T-cell engager targeting CD20 and CD3) and polatuzumab vedotin (an antibody-drug conjugate that targets CD79b protein) with a standard-of-care chemoimmunotherapy with rituximab plus gemcitabine, oxaliplatin (GemOx) for patients with relapsed large B-cell lymphoma,” stated Dr. Vose. The experimental arm of mosunetuzumab plus polatuzumab vedotin demonstrated an improved overall response rate of 70.3% vs 40.0% with rituximab plus GemOx.
“The most impressive part of the data was that 75% of the patients with a complete response to mosunetuzumab plus polatuzumab vedotin were still in remission at 1 year,” Dr. Vose told The ASCO Post. “The toxicity of mosunetuzumab plus polatuzumab vedotin is manageable and low grade, which enables patients to stay on therapy longer if needed for a bridge to alternative therapy. For example, this combination is sometimes used as a bridge to chimeric antigen receptor T-cell transplant or can be used as a regimen during relapse without a plan for transplantation. The mosunetuzumab plus polatuzumab vedotin combination represents a low-toxicity alternative option for our patients who have failed to respond to standard chemoimmunotherapy. As this regimen gets additional use, other patient populations may also benefit from it,” she concluded.
DISCLOSURE: Dr. Vose has received clinical research support from AbbVie, Bristol Myers Squibb, Epizyme, Genmab, Kite Pharma, Loxo, Novartis, and Seagen; and has served as a consultant or advisor to AbbVie, Adaptive Biotechnologies, AstraZeneca, Genmab, Novartis, Pfizer/Hospira.
