Carfilzomib in combination with R-CHOP for initial treatment of patients with non-germinal center diffuse large B-cell lymphoma: a multicenter, single arm, phase 1/2 study.

We performed a phase I/II trial to explore the safety and efficacy of carfilzomib (K) in combination with R-CHOP (KR-CHOP) in patients with diffuse large B cell lymphoma (DLBCL). A total of 48 patients were enrolled and 47 were treated. The overall response rate (ORR) was 89% (70% complete response). At a median follow-up of 31 months, 3-year Kaplan-Meier estimates of PFS and OS were 79% and 87%, respectively. Treatment with KR-CHOP for non-GC DLBCL was associated with a decreased risk of disease progression and death relative to standard of care treatment with R-CHOP with hazard ratios (HR) of 0.16 [95% confidence interval (CI) 0.04-0.58, p = 0.002] and 0.31 [(95% CI, 0.09 - 0.99), p = 0.02], respectively. The most common grade 3 or 4 adverse events (AEs) were anemia (13%), thrombocytopenia (9%) and febrile neutropenia (9%). KR-CHOP is safe and may have preferential activity in non-GC DLBCL.