Acalabrutinib and its use in treatment of chronic lymphocytic leukemia

Future Oncol. 2019 Feb;15(6):579-589. doi: 10.2217/fon-2018-0637. Epub 2018 Nov 1.


Acalabrutinib received an accelerated US FDA approval for patients with relapsed/refractory mantle cell lymphoma in 2017 and is currently being evaluated in chronic lymphocytic leukemia (CLL). To date, ibrutinib is the only Bruton tyrosine kinase (BTK) inhibitor that's approved for treatment of CLL. Acalabrutinib is a second generation BTK inhibitor that binds covalently to the Cys481 residue on BTK and has half maximal inhibitory concentration (IC50) of 3 nM. In preclinical mouse models, acalabrutinib significantly reduced proliferation of CLL cells. Results of Phase I/II trials revealed overall response rates (ORR) of 96% in treatment-naive, 93% in relapsed/refractory and 76% in ibrutinib intolerant patients with CLL. The most common adverse effects (>20%) were grade 1-2 comprising constitutional symptoms, GI toxicity, rash and myelosuppression. There were limited grade 3 or 4 toxicities, involving syncope, pneumonia, hypertension, atrial fibrillation, neutropenia and thrombocytopenia.

Keywords: ACP-196; BTK inhibitors; acalabrutinib; atrial fibrillation; bleeding; chronic lymphocytic leukemia; ibrutinib; infection; obinutuzumab.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Benzamides / administration & dosage
  • Benzamides / adverse effects
  • Benzamides / pharmacokinetics
  • Benzamides / therapeutic use*
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Pyrazines / pharmacokinetics
  • Pyrazines / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents
  • Benzamides
  • Protein Kinase Inhibitors
  • Pyrazines
  • acalabrutinib