[Recommendations from the French CML Study Group (Fi-LMC) for BCR-ABL1 kinase domain mutation analysis in chronic myeloid leukemia]

Abstract

In the context of chronic myeloid leukemia (CML) resistant to tyrosine kinase inhibitors (TKIs), BCR-ABL1 tyrosine kinase domain (TKD) mutations still remain the sole biological marker that directly condition therapeutic decision. These recommendations aim at updating the use of BCR-ABL1 mutation testing with respect to new available therapeutic options and at repositioning different testing methods at the era of next generation sequencing (NGS). They have been written by a panel of experts from the French Study Group on CML (Fi-LMC), after a critical review of relevant publications. TKD mutation testing is recommended in case of treatment failure but not in case of optimal response. For patients in warning situation, mutation testing must be discussed depending on the type of TKI used, lasting of the treatment, kinetic evolution of BCR-ABL1 transcripts along time and necessity for switching treatment. The kind and the frequency of TKD mutations occasioning resistance mainly depend on the TKI in use and disease phase. Because of its better sensitivity, NGS methods are recommended for mutation testing rather than Sanger's. Facing a given TKD mutation, therapeutic decision should be taken based on in vitro sensitivity and clinical efficacy data. Identification by sequencing of a TKD mutation known to induce resistance must lead to a therapeutic change. The clinical value of testing methods more sensitive than NGS remains to be assessed.

Keywords: ABL1 inhibitors; ABL1 tyrosine kinase domain mutations; Chronic myeloid leukemia; Inhibiteurs d’ABL1; Leucémie myéloïde chronique; Mutations du domaine tyrosine kinase d’ABL1; Resistance; Résistance.