Asciminib for chronic myeloid leukaemia: Next questions

Br J Haematol. 2022 Nov;199(3):322-331. doi: 10.1111/bjh.18323. Epub 2022 Jun 21.

Abstract

Recent approval of asciminib, a novel "specifically targeting the ABL myristoyl pocket" (STAMP) BCR-ABL1 inhibitor, for the treatment of chronic myeloid leukaemia (CML) patients who have either failed ≥2 lines of therapy or have the T315I mutation, has provided clinicians with a wider selection of potentially effective treatment options. Asciminib has the attractive twin attributes of high potency directed against BCR-ABL1 and good tolerability based on its limited off-target effects. However, it is unclear exactly where asciminib will be positioned amongst the other available tyrosine kinase inhibitors (TKIs), especially ponatinib which is also available for the same indications. There are many questions yet to be answered with regard to the optimal use of asciminib which include its role in the first- and second-line settings, combination therapy with other TKIs, and effectiveness in advanced phase CML. In this review, we discuss the available data on asciminib while exploring a number of clinical trials in progress. Finally, we provide our opinion based on the current data about where asciminib is most likely to be the optimal choice, which will hopefully assist clinicians with therapy selection.

Keywords: BCR-ABL; CML; new drugs for leukaemia.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • asciminib
  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl
  • Antineoplastic Agents