Risk factors and reasons for switching from front-line therapy in the Italian chronic myeloid leukaemia network: A cohort study.

Identifying chronic myeloid leukaemia (CML) patients at risk of therapeutic switch remains debated. We analysed the cumulative risk of treatment change in the CML Italian network prospective cohort based on first-line tyrosine kinase inhibitors and patient characteristics. Sub-hazard ratios (sHRs) were estimated using Fine and Gray multivariable models. Among 1662 patients, initial treatment consisted of imatinib for 840 (50.5%), nilotinib for 490 (29.5%) and dasatinib for 332 (20.0%). Subsequently, 492 patients (29.6%) required second-line therapy, with 232 (47.1%) switching due to resistance and 176 (35.8%) due to intolerance. At 2 years, the risk of resistance was 18.3% for imatinib, 8.4% for dasatinib (sHR = 0.32; 95% confidence interval 0.21-0.49) and 6.8% for nilotinib (0.29; 0.19-0.42). The risk of switching increased in intermediate (1.95; 1.40-2.72) and high Eutos long term survival (ELTS) risk (3.19; 2.10-4.83) but was reduced with older age (0.97 per year; p < 0.0001). Intolerance at 2 years was 8.5% for imatinib, 12.4% for dasatinib (2.55; 1.73-3.75) and 5.2% for nilotinib (1.04; 0.65-1.65). Switching to a third-line therapy at 3 years was 8% for imatinib, 5% for dasatinib and 4% for nilotinib. The results showed that the time to first treatment switch for resistance is shorter for younger patients, for imatinib and for intermediate/high ELTS risks. The risk of switching for intolerance is higher for patients initially treated with dasatinib.