The preclinical discovery and development of acalabrutinib for the treatment of mantle cell lymphoma.

INTRODUCTION

Over the past decade, Bruton's tyrosine kinase (BTK) inhibitors have been approved for clinical use in several indolent B-cell lymphoid malignancies, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia. Among these, acalabrutinib is a second-generation covalent, irreversible BTK inhibitor that demonstrates higher selectivity and non-inferior efficacy than ibrutinib.

AREAS COVERED: This paper reviews recent developments in the use of acalabrutinib in treatment-naïve and relapsed/refractory mantle cell lymphoma (MCL). Google Scholar and PubMed were initially searched for articles in English, published from 2017 to February 2026. The reference lists of the articles were then searched again. In addition, a manual search was performed of conference proceedings from the last 5 years of The American Society of Hematology, American Society of Clinical Oncology and the European Hematology Association.

EXPERT OPINION: Acalabrutinib is approved by FDA for the treatment of previously treated and relapsed/refractory patients with MCL. While it has been found to demonstrate high activity and good tolerability as a single drug and in combination with other agents, further clinical trials are required to optimize its use in MCL and other lymphomas.