Durable Responses from 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

Introduction: R‐CHOP remains the standard of care for DLBCL yet many patients (pts.) either fail to respond or relapse after having achieved an initial remission. Dysregulation of B Cell receptor (BCR) signalling is well recognised in some sub-types of DLBCL. In the phase III PHOENIX study (NCT01855750), the addition of the Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib (I) to R‐CHOP (R‐CHOP‐I) did not improve the outcome of the study population with non‐germinal centre like DLBCL. However, R‐CHOP‐I treated pts. who were aged less than 60 years had a significantly improved progression free survival (PFS) and overall survival (OS) compared to those receiving R‐CHOP alone. In pts. aged over 60 years, the addition of I increased toxicity and compromised the delivery of R‐CHOP. Acalabrutinib (A) is a second generation BTKi, with enhanced kinase selectivity and potential for better efficacy and tolerability over first‐generation inhibitors. There is a strong rationale to combine A with R‐CHOP in untreated de novo DLBCL to understand its safety profile and efficacy.