Incorporating acalabrutinib, a selective next-generation Bruton tyrosine kinase inhibitor, into clinical practice for the treatment of haematological malignancies

Br J Haematol. 2021 Apr;193(1):15-25. doi: 10.1111/bjh.17184. Epub 2020 Nov 20.

Abstract

Greater understanding of the mechanisms involved in the disease progression of haematological malignancies has led to the introduction of novel targeted therapies with reduced toxicity compared with chemotherapy-based regimens, which has expanded the treatment options for patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Ibrutinib is a first-in-class Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of patients with CLL/SLL or relapsed/refractory MCL. However, next-generation BTK inhibitors have been developed with improved specificity and the potential to reduce the off-target toxicity observed with ibrutinib. Acalabrutinib is a highly selective, next-generation BTK inhibitor, which was granted accelerated approval by the US Food and Drug Administration in 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. In November 2019, it was also granted approval for the treatment of adult patients with CLL/SLL on the basis of two phase 3 clinical trials. This review describes the current understanding of acalabrutinib according to clinical study data for the treatment of MCL and CLL/SLL and shares recommendations from our practice on how it should be used when treating patients in the clinic, including dosing, administration and management of adverse events.

Keywords: BTK inhibitors; Bruton tyrosine kinase; acalabrutinib; chronic lymphocytic leukaemia; mantle cell lymphoma.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors*
  • Aged
  • Aged, 80 and over
  • Benzamides / adverse effects
  • Benzamides / pharmacology
  • Benzamides / therapeutic use*
  • Clinical Trials as Topic
  • Disease Progression
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / pathology
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Lymphoma, Mantle-Cell / drug therapy*
  • Middle Aged
  • Piperidines / adverse effects*
  • Piperidines / therapeutic use
  • Practice Patterns, Physicians'
  • Pyrazines / adverse effects
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use*
  • Safety
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration / legislation & jurisprudence

Substances

  • Benzamides
  • Piperidines
  • Pyrazines
  • ibrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • acalabrutinib
  • Adenine