Multicenter phase 1b-2 study of first-line acalabrutinib plus R-CHOP for diffuse large B-cell lymphoma

Acalabrutinib is a second-generation BTK inhibitor with efficacy in relapsed and refractory diffuse large B-cell lymphoma (DLBCL). The phase 1b-2 ACCEPT study, at seven centers in the UK, evaluated acalabrutinib in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) as first-line therapy for DLBCL. The primary endpoint was to determine the recommended phase 2 dose (RP2D) of acalabrutinib and assess safety and overall response rate (ORR). Among 31 patients (median age 64 years, range 24-80; 76% stage III/IV; 55% IPI ≥ 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 the 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 of 24 patients (83%) had a complete response and three (12.5%) a partial response, for an ORR of 96% (95% CI 79-100). With median 30-months follow-up, the 24-month rates of progression-free survival, event-free survival, and overall survival were 95% (95% CI 68-99), 90% (66-97), and 96% (73-99), respectively. The authors conclude that the combination of first-line acalabrutinib with R-CHOP is well tolerated among DLBCL patients, including in those older than 65 years.