Ibrutinib plus venetoclax (ABT-199) improves outcomes over standard therapy in patients with mantle-cell lymphoma (MCL) and a poor prognosis reports a new research in the New England Journal of Medicine.

 MCL is currently managed with targeted therapy for B-cell neoplasms, which includes ibrutinib, a BTK inhibitor, and venetoclax, an inhibitor of BCL2. Each had a complete response rate (CRR) of 21% in previous studies. Preclinical models signify that dual inhibition of BTK and BCL2 is synergistic. Moreover, the agents have overlapping adverse events (AEs) that are usually insignificant.

Constantine S. Tam, MD, from the Peter MacCallum Cancer Centre at the Royal Melbourne Hospital in Melbourne, Australia led this ABT-199 and Ibrutinib in Mantle-Cell Lymphoma (AIM) study which was an open-label, single-group, phase 2 study that examined the combination therapy of ibrutinib plus venetoclax in patients with MCL.

Adults with relapsed or refractory MCL and those who were not candidates for cytotoxic chemotherapy were also eligible for the study.

Monotherapy with oral ibrutinib 560mg daily was given for four weeks to reduce the risk of tumor lysis syndrome (TLS). Venetoclax 50mg was added in week five, and the dose was increased in a systematic, weekly manner to 400 mg orally per day. The recommended dose for treating chronic lymphocytic leukemia (CLL) was decided when the study commenced. Based on an updated recommendation for MCL, the protocol was amended to allow escalation to venetoclax 800mg per day after week 16 if there was no complete response.

Calculating the tumor size and the lymphocyte count, risk stratification for TLS was based on studies of venetoclax in patients with CLL. The recommended dose was amended to incorporate a supplementary ramp-up week of venetoclax 20mg daily after two of 15 patients developed TLS.