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CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions

  • Chronic Myeloid Leukemias (V Oehler, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The clinical scenario for chronic myeloid leukemia patients rapidly changed after the introduction of tyrosine kinase inhibitors (TKIs). Second-generation TKIs as frontline treatment increased the rate of deep molecular responses without increasing the rate of overall survival. About 20% of patients experience resistance to these agents, needing alternative treatments. Here, we reviewed the possible mechanisms of resistance, available treatment, and new drugs developed to counteract and overcome resistance.

Recent Findings

Results of novel TKIs have been recently reported, especially for the setting of T315I mutated patients, such as olverembatinib and asciminib, or for patients who developed resistance due to other mutations, such as vodobatinib. Most of new TKIs are selected among compounds tested selective on ABL, therefore without possible off-target effects in the long term.

Summary

New potential treatments are on the horizon in the field of CML, able to rescue patients treated firstly with one or more second-generation TKIs. Results of ongoing trials and real-world evidence dataset will help us to identify the appropriate timing of intervention and to select appropriate candidate to these drugs.

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Authors and Affiliations

  1. Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Via Benevento 6, 00161, Rome, Italy

    Emilia Scalzulli, Ida Carmosino, Maria Laura Bisegna, Maurizio Martelli & Massimo Breccia

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  1. Emilia Scalzulli
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  2. Ida Carmosino
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  3. Maria Laura Bisegna
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Correspondence to Massimo Breccia.

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MB received honoraria by Novartis, Incyte, Pfizer, BMS/Celgene, and AbbVie. All the other authors have no conflict of interest.

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Scalzulli, E., Carmosino, I., Bisegna, M.L. et al. CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions. Curr Hematol Malig Rep 17, 198–205 (2022). https://doi.org/10.1007/s11899-022-00683-3

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