Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a Phase II study

This Phase II study evaluated mosunetuzumab plus cyclophosphamide, doxorubicin, prednisone, and polatuzumab vedotin (Pola-M-CHP) versus Pola-rituximab (R)-CHP for first-line treatment of diffuse large B-cell lymphoma (DLBCL). Patients were randomized 2:1 to receive 6 cycles of Pola-M-CHP or Pola-R-CHP on Day 1 of each 21-day cycle. Mosunetuzumab was administered intravenously via step-up dosing during Cycle 1 and at 30 mg on Day 1 of subsequent cycles. The primary endpoint was Independent Review Committee-assessed complete response (CR) rate by positron emission tomography-computed tomography. Overall, 62 patients were enrolled and received Pola-M-CHP (n = 40) or Pola-R-CHP (n = 22). CR rates were similar in both arms (72.5% with Pola-M-CHP versus 77.3% with Pola-R-CHP); the 24-month investigator-assessed progression-free survival rate was 70.8% (95% CI, 55.6-86.1) with Pola-M-CHP versus 81.8% (95% CI, 65.7-97.9) with Pola-R-CHP. The most common adverse event (AE) was cytokine release syndrome (68.4%; mostly Grade 1 [52.6%], and primarily confined to Cycle 1) with Pola-M-CHP and neutropenia/neutrophil count decreased (54.5%) with Pola-R-CHP. Neutropenia/neutrophil count decreased was the most frequently observed Grade ≥3 AE in both arms (Pola-M-CHP: 36.8%; Pola-R-CHP: 22.7%). Rates of Grade ≥3 AEs (86.8% versus 59.1%), serious AEs (63.2% versus 13.6%), and AEs leading to treatment discontinuation (13.2% versus 0%) were higher with Pola-M-CHP than Pola-R-CHP, respectively. Pharmacodynamic changes were supportive of mosunetuzumab's mechanism of action and its addition to the Pola-CHP combination. Pola-M-CHP, although an active combination, did not demonstrate a clinical benefit over Pola-R-CHP in this small study. This trial was registered at www.clinicaltrials.gov as #NCT03677141.