ASH 2025 | Mechanisms of resistance to TKIs in CML
Massimo Breccia, MD, Sapienza University of Rome, Rome, Italy, discusses the main mechanisms of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). Dr Breccia highlights that a proportion of patients may develop kinase domain mutations, while other mechanisms of resistance involve epigenetic changes or remain unknown. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript
Several mechanisms of resistance have been observed in CML. Most of them, 40-60% of the patients may develop kinase domain mutations, but some other mechanisms of resistance are indeed associated with epigenetic mechanisms or other mechanisms are unknown, still unknown, some important mechanisms can be rescued by switching the patients to another line of treatment, so we perform an analysis in Italy collecting information in 1,500 patients collected into our Italian CML network...
Several mechanisms of resistance have been observed in CML. Most of them, 40-60% of the patients may develop kinase domain mutations, but some other mechanisms of resistance are indeed associated with epigenetic mechanisms or other mechanisms are unknown, still unknown, some important mechanisms can be rescued by switching the patients to another line of treatment, so we perform an analysis in Italy collecting information in 1,500 patients collected into our Italian CML network. And we found the reason for resistance in 492 patients overall, but of them 270 switched for resistance. In particular, we found an inverse correlation with increasing age and possibility of resistance. We found indeed also a decreased rate of resistance due to second-generation TKs as compared to imatinib. Imatinib after only two years of median follow-up is 30%. Indeed we found an increased rate of intolerance to dasatinib and in particular, as demonstrated also by other groups, intermediate and high-risk patients with a long-term survival score, increased rate of possible resistance.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
