Mosunetuzumab Plus Polatuzumab Vedotin in Transplant-Ineligible Refractory/Relapsed Large B-Cell Lymphoma: Primary Results of the Phase III SUNMO Trial.

Abstract

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. In the phase III SUNMO trial, patients with refractory/relapsed LBCL who were ineligible for autologous stem-cell transplant were randomly assigned (2:1) to receive Mosun-Pola or rituximab, gemcitabine, and oxaliplatin (R-GemOx). Dual primary end points were centrally assessed overall response rate (ORR) and progression-free survival (PFS). Overall survival was a key secondary end point. A total of 208 patients were randomly assigned 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 PFS was significantly longer with Mosun-Pola than with R-GemOx (11.5 months [95% CI, 5.6 to 18] <i>v</i> 3.8 months [95% CI, 2.9 to 4.1]; hazard ratio for progression or death, 0.41 [95% CI, 0.3 to 0.6]; <i>P</i> < .0001). ORR was significantly greater with Mosun-Pola versus R-GemOx (70% <i>v</i> 40%; <i>P</i> < .0001), with complete response rates of 51% and 24%, respectively. In the Mosun-Pola group, the rate of grade ≥2 cytokine release syndrome (CRS) and usage of tocilizumab occurred in <5% of patients and patient-reported outcomes were improved compared with R-GemOx. Mosun-Pola demonstrated superior efficacy versus R-GemOx, with significant improvements in both ORR and PFS, and infrequent CRS events with a manageable safety profile.