Efficacy and safety of subcutaneous mosunetuzumab plus polatuzumab vedotin in patients with relapsed/refractory large B-cell lymphoma: Japan subgroup analysis of the phase III SUNMO trial

Background: Novel, accessible treatment options, are needed for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Mosunetuzumab, a T-cell–engaging bispecific antibody, plus polatuzumab vedotin, an antibody–drug conjugate, (Mosun-Pola), represents a novel fixed-duration outpatient therapy. The phase III SUNMO study (NCT05171647) demonstrated superior efficacy of Mosun-Pola versus rituximab plus gemcitabine-oxaliplatin (R-GemOx) in patients with R/R LBCL, with a manageable safety profile. We report outcomes of a Japan subgroup analysis of the SUNMO study. Methods: Patients were randomized 2:1 to receive Mosun-Pola or R-GemOx. Dual primary endpoints were centrally assessed overall response rate and progression-free survival (PFS). Results: At data cutoff (February 17, 2025), of 208 patients randomized (Mosun-Pola, n = 138; R-GemOx, n = 70), 16 were enrolled from Japan (Mosun-Pola, n = 9; R-GemOx, n = 7). All patients receiving Mosun-Pola achieved a response (100% [n = 9]) versus 57.1% (n = 4/7) for those receiving R-GemOx. PFS was significantly prolonged with Mosun-Pola; median PFS of 16.2 months versus 3.8 months with R-GemOx (hazard ratio: 0.42; 95% confidence interval: 0.07–2.63). In the safety-evaluable population (Mosun-Pola, n = 9; R-GemOx, n = 7), overall incidence of adverse events was similar between the Japan subgroup and the overall population across both treatment arms. Cytokine release syndrome occurred in 5 patients who received Mosun-Pola; all events were grade 1, and all resolved. No incidence of immune effector cell-associated neurotoxicity syndrome was reported. Conclusions: Mosun-Pola demonstrated promising efficacy and manageable safety in patients with R/R LBCL enrolled from Japan, which was comparable with the overall population, supporting Mosun-Pola as a potential new treatment option in this patient population. Clinical trial registration: ClinicalTrials.gov, NCT05171647.