Sequential TKI Treatment in Patients With Chronic Phase Chronic Myeloid Leukemia Resistant to Frontline Nilotinib or Dasatinib Therapy. A Real-Life Survey From the Italian Campus CML Network.

Authors

Gabriele Gugliotta, Mario Annunziata, Isabella Capodanno, Davide Rapezzi, Immacolata Attolico, Marianna Caramella, Iolanda D Vincelli, Antonella R Rossi, Mario Tiribelli, Alessandra Malato, Michele Cimminiello, Vincenzo Accurso, Massimiliano Bonifacio, Sara Galimberti, Giuseppina Loglisci, Elisabetta Abruzzese, Monica Bocchia, Antonella Gozzini, Micaela Bergamaschi, Maria C Miggiano, Agostino Tafuri, Grazia Sanpaolo, Anna R Scortechini, Monica Crugnola, Debora Luzi, Luigiana Luciano, Gianni Binotto, Roberto Latagliata, Fausto Castagnetti, Alessandro Allegra, Giorgina Specchia, Uros Markovic, Gianantonio Rosti, Robin Foà, Giuseppe Saglio, Massimo Breccia, Fabio Stagno

Published in

Clinical lymphoma, myeloma & leukemia. Jul 24, 2026. Epub Jul 24, 2026.

Abstract

Limited information is available on the management and outcome of chronic myeloid leukemia (CML) patients who are resistant to first-line treatment with a second-generation tyrosine kinase inhibitor (2G-TKI).
We conducted a multicenter, real-world, retrospective analysis on 69 chronic phase (CP) CML patients who switched to second-line treatment in case of failure (according to the European LeukemiaNet 2020 recommendations) after first-line nilotinib or dasatinib.
The median time to switch to second-line therapy was 15 months, and ponatinib was the most frequently used TKI (68%). As best molecular response (MR), 78% of patients achieved a BCR::ABL1^IS transcript level <1%. The estimated 3-year cumulative incidence of MR3 was 69.4% (95% CI, 53.2%-84.2%). Thirty percent of patients, after a median time of 9 months from the start of second-line treatment, received a third-line treatment, mainly because of resistance (81%). As the best MR to third-line TKI, 50% of patients obtained a BCR::ABL1^IS transcript level <1%. Overall, 9% of patients proceeded to stem-cell transplantation. Progression to blast phase occurred in 7% of patients, and all of them died. An additional patient died because of heart failure. The estimated 5-year progression-free survival and overall survival were 87% (95% CI, 67.1%-95.2%) and 83% (95% CI, 61.7%-93%), respectively. The MR at the last contact was ≥MR4 in 30% and MR3 in 22% of patients.
Our analysis highlights that sequential treatment in patients with CP-CML resistant to frontline 2G-TKIs therapy is feasible and can be effective in a relevant proportion of patients.

PMID:
42608256
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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