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. 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.

CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions / Scalzulli, Emilia; Carmosino, Ida; Bisegna, Maria Laura; Martelli, Maurizio; Breccia, Massimo. - In: CURRENT HEMATOLOGIC MALIGNANCY REPORTS. - ISSN 1558-8211. - 17:6(2022), pp. 198-205. [10.1007/s11899-022-00683-3]

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

Scalzulli, Emilia;Bisegna, Maria Laura;Martelli, Maurizio;Breccia, Massimo
2022

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. 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.
2022
Chronic myeloid leukemia; Intolerance; New drugs; Resistance; Second-generation TKIs
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions / Scalzulli, Emilia; Carmosino, Ida; Bisegna, Maria Laura; Martelli, Maurizio; Breccia, Massimo. - In: CURRENT HEMATOLOGIC MALIGNANCY REPORTS. - ISSN 1558-8211. - 17:6(2022), pp. 198-205. [10.1007/s11899-022-00683-3]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1664881
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