A multicenter phase II study of glofitamab plus polatuzumab-R-CHP for patients with diffuse large B-cell lymphoma.

In this phase II trial, we evaluated the addition of the CD3xCD20 bispecific antibody, glofitamab (glofit) to polatuzumab, rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and an international prognostic index (IPI) ³ 2. Patients received two cycles of pola-R-CHP (one cycle of R-CHOP allowed). Glofitamab was added to pola-R-CHP during cycles 3 through 6 and used as monotherapy for cycles 7 and 8. The primary objective was the best complete response (CR) rate. A total of 41 patients enrolled. The median age was 61 years (range 35-86), and 59% were male. IPI scores were 2 (39%), 3 (41%), and 4 (20%), and 86% of patients had stage III/IV disease. Most patients had DLBCL, NOS (78%) and 12% had high grade B-cell lymphoma with translocations in MYC and BCL-2 and/or BCL-6. The best CR rate was 95% (39/41) (95% CI: 83-99) and both patients with a partial response at the end of therapy converted to CR without intervention. With a median follow-up of 23.9 months, the median progression-free survival (PFS) has not been reached and the 24-month PFS was 95% (95% CI: 89-100). Four (10%) patients developed cytokine release syndrome (CRS) (all grade 1), and no immune effector cell-associated neurotoxicity syndrome (ICANS) was reported. Glofit-pola-R-CHP resulted in high rates of CR and preliminary evidence of durable responses and the schedule, with delayed incorporation of glofit, resulted in low rates of CRS and no neurotoxicity. These data support further evaluation of this regimen. NCT05800366.