Treatment-free remission in chronic myeloid leukemia

Matteo Molica, Kiran Naqvi, Jorge E. Cortes, Shilpa Paul, Tapan M. Kadia, Massimo Breccia, Hagop Kantarjian, Elias J. Jabbour

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Tyrosine kinase inhibitors (TKIs) represent a major breakthrough in the treatment of chronic myeloid leukemia (CML). Thanks to these agents, CML has been transformed from a disease with limited treatment options and a dismal prognosis into a more indolent disease with survival comparable to that of the general population. The need for ongoing TKI therapy remains controversial for several reasons, including cost and toxicity. Studies in CML patients with a sustained deep molecular response have demonstrated that stopping TKI therapy is feasible and safe. Given the heterogeneity of results reported in clinical trials, practice guidelines for optimal patient selection and proper monitoring after discontinuation of TKIs are proposed outside of clinical trials. Current data available show that 40% to 60% of patients who stop therapy relapse; molecular relapses typically occur within 6 months, but nearly all relapsing patients regain response upon reinitiation of the TKI. Several factors that predict for relapse have been investigated. Duration of prior TKI therapy, achievement of deep molecular response, depth of molecular response, prior interferon treatment, and Sokal risk score have been shown to be potential predictors for relapse. Leukemia stem cells that are resistant to TKIs, and that persist despite undetectable BCR/ ABL1 transcript levels, likely are responsible for disease relapse after discontinuation. Efforts geared toward better identification of low levels of BCR/ABL1 transcript using new techniques such as digital polymerase chain reaction, along with eradicating CML clones using combination therapies with agents such as pegylated interferon or venetoclax with TKIs, will hopefully lead to a functional cure of this disease.

Original languageEnglish (US)
Pages (from-to)686-696
Number of pages11
JournalClinical Advances in Hematology and Oncology
Volume17
Issue number12
StatePublished - Dec 2019

Keywords

  • Chronic myeloid leukemia
  • Deep molecular response
  • Treatment-free remission
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Hematology
  • Oncology

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