Mosunetuzumab plus polatuzumab vedotin in transplant-ineligible refractory/relapsed large B-cell lymphoma: primary results of the phase 3 SUNMO trial.

Abstract

PURPOSE Prognosis for patients with refractory/relapsed large B-cell lymphoma (LBCL) considered ineligible for curative-intent therapy is poor. The combination of mosunetuzumab, a T-cell-engaging bispecific antibody, and polatuzumab vedotin, an antibody-drug conjugate, (Mosun-Pola), represents a novel fixed-duration outpatient therapy. METHODS In the phase 3 SUNMO trial, patients with refractory/relapsed LBCL who were ineligible for autologous stem cell transplant were randomized (2:1) to receive Mosun-Pola or rituximab, gemcitabine, and oxaliplatin (R-GemOx). Dual primary endpoints were centrally-assessed overall response rate and progression-free survival. Overall survival was a key secondary endpoint. RESULTS A total of 208 patients were randomized to receive Mosun-Pola (n=138) or R-GemOx (n=70). At a median follow-up of 23.2 months, the primary analysis of SUNMO demonstrated that the median progression-free survival was significantly longer with Mosun-Pola than with R-GemOx(11.5 months [95% confidence interval (CI), 5.6-18] vs 3.8 months [95% CI, 2.9-4.1]; hazard ratio for progression or death, 0.41 [95% CI, 0.3-0.6]; P<0.0001). Overall response rate was significantly greater with Mosun-Pola versus R-GemOx (70% vs 40%; P<0.0001), with a complete response rate of 51% and 24%, respectively. In the Mosun-Pola group, the rate of grade ≥2 cytokine release syndrome and usage of tocilizumab occurred in less than 5% of patients, and patient-reported outcomes were improved compared with R-GemOx. CONCLUSION Mosun-Pola demonstrated superior efficacy verus R-GemOx, with significant improvements in both overall response rate and progression-free survival, and infrequent cytokine release syndrome events with a manageable safety profile.(Funded by F. Hoffmann-La Roche Ltd; ClinicalTrials.gov, NCT05171647).