Acalabrutinib in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) was well tolerated and may improve efficacy for patients with untreated diffuse large B-cell lymphoma (DLBCL), according to a study presented at the 2020 ASH Annual Meeting.
The study included treatment-naïve patients with histologically confirmed DLBCL who received six cycles of R‐CHOP plus acalabrutinib in cycles two through six. In a continuation phase, patients received acalabrutinib only for two 28-day cycles after R-CHOP.
The primary objective of the phase Ib study was to establish a recommended phase II dose of acalabrutinib in combination with R‐CHOP (modified classical 6+6 design). Phase II assessed the overall response rate (ORR) of the combination and safety outcomes. Between May 2017 and January 2020, 38 patients (median age, 64 years; range, 24-80 years; 39% were >65 years) were enrolled. Most (74%) had stage III/IV disease, and 26% had high International Prognostic Index scores. Seven patients were ultimately ineligible for the study.
Researchers observed no dose-limiting toxicities, and the maximum tolerated dose of acalabrutinib was not reached. The recommended phase II dose was acalabrutinib 100 mg twice daily.
The most common grade ≥3 adverse events (AEs) were neutropenia (26%), febrile neutropenia (13%), and diarrhea (11%), and the most common serious AE was febrile neutropenia (13%). Age did not impact patients’ ability to receive full doses of R-CHOP plus acalabrutinib. One patient in the first cohort who was receiving acalabrutinib 100 mg progressed on therapy and ultimately died.
Among 24 eligible patients who received the acalabrutinib 100 mg twice daily in either the dose escalation or expansion phase, 22 patients have responded to treatment. Four patients withdrew early from treatment and were included in the efficacy analysis.
The ORR was 95%, with 82% of patients achieving a metabolic complete response (CR), including three partial responses and one with stable disease. One patient with MYC/BCL2/BCL6 rearrangements and one with MYC/BCL2 rearrangement achieved a metabolic CR, neither of whom have progressed on treatment.
Twelve-month progression-free and overall survival were both 100% in patients who received the recommended phase II dose of acalabrutinib. R-CHOP did not affect the pharmacokinetics of acalabrutinib, according to the authors.
This treatment combination should be explored in randomized trials, the researchers noted.
Davies A, Caddy J, Mercer K, et al. Acalabrutinib in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) As First Line Therapy for Patients with Diffuse Large B-Cell Lymphoma (DLBCL): The Accept Phase Ib/II Single Arm Study. Abstract 1185. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, December 2-11, 2020.