Acalabrutinib in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone as First-Line Therapy for Patients With Diffuse Large B-Cell Lymphoma

PURPOSE Acalabrutinib, a second-generation Bruton tyrosine kinase inhibitor, has efficacy in relapsed and refractory diffuse large B-cell lymphoma (DLBCL). The ACCEPT trial investigated the safety and efficacy of acalabrutinib in addition to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) in first-line therapy. METHODS In this phase Ib/II non-randomized study, eligible patients were treatment naïve, aged 16 years or older with a histologic diagnosis of DLBCL. The primary end point of the trial was to determine the recommended phase II dose (RP2D) of acalabrutinib in combination with R-CHOP and assess the safety and overall response rate (ORR). RESULTS Between 2017 and 2020, 38 patients were enrolled. Of those enrolled, seven were ineligible. Median age was 64 years (range, 24-80); 76% were stage III/IV; 55% International Prognostic Index ≥3. No dose-limiting toxicities were observed, and the RP2D of acalabrutinib was 100 mg twice daily. The most common grade ≥3 adverse events at RP2D were neutropenia (37%), febrile neutropenia (13%), and diarrhea (10%). Eighty-eight percent of patients received six cycles of R-CHOP. Age did not compromise treatment delivery. At the RP2D, 20/24 (83%) patients had a complete response and three (12.5%) a partial response (ORR, 96% [95% CI, 79 to 100]). With median 30-months follow-up, the 24-month progression-free survival was 95% (95% CI, 68 to 99), event-free survival was 90% (95% CI, 66 to 97), and overall survival was 96% (95% CI, 73 to 99). CONCLUSION The combination of acalabrutinib with R-CHOP is well tolerated, including in those older than 65 years. High efficacy in DLBCL was observed, regardless of cell-of-origin subtype. These findings support further investigation of this combination in a randomized trial.