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

Background: 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). Patients and Methods: 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. Results: 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::ABL1IS 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::ABL1IS 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. Conclusion: 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.