A Multicenter Retrospective Chart Review Study of Treatment and Disease Patterns and Clinical Outcomes of Patients with Chronic-Phase Chronic Myeloid Leukemia in Third-Line Treatment or with T315I Mutation

SIMPLE SUMMARY: Many patients with chronic-phase chronic myeloid leukemia (CP-CML) treated with a tyrosine kinase inhibitor (TKI) experience disease progression and switch to another TKI, but each switch yields diminishing returns. To gain insight into the burden of repeated TKI treatment failures, this study analyzed the characteristics, treatment and disease patterns, and outcomes of adult patients with CP-CML in France whose disease progressed after treatment with two or more TKIs between 2006 and 2021. Patients switched TKIs up to six times; in many cases, treatment with the first and second TKIs lasted <2 years. On the other hand, patients who showed a good response to their third TKI had a lower risk of death. These findings provide a broad view of CP-CML treatment in France over the last 15 years and highlight the need for more effective therapies early in the treatment course that can improve outcomes for patients with CP-CML. ABSTRACT: This retrospective chart review study investigated the clinical burden of adult patients with chronic-phase chronic myeloid leukemia (CP-CML) treated at three centers in France (2006–2021) who failed on two or more tyrosine kinase inhibitors (TKIs; third-line [3L]+ cohort) or harbored the BCR::ABL1 T315I mutation (T315I cohort). In the 3L+ cohort (N = 157; median age at diagnosis, 56 years), TKIs received in 3L (median duration: 17 months) were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Of the 145 patients with documented responses in 3L, 42% experienced major molecular response (MMR) at 12 months. Median event-free survival [95% confidence interval] was 53.6 [44.0, 67.5] months, and median progression-free survival and overall survival (OS) were not reached. Achieving MMR in 3L was associated with a decreased mortality risk. In the T315I cohort (N = 17; 52 years), 41% of patients received five or more lines of therapy. Following identification of the T315I mutation, ponatinib was the most common TKI used (59%); the median [interquartile range] OS was 5 [3–10] years. The most common adverse events were infections (3L+ cohort) and thrombocytopenia (T315I cohort) (both 18%). Well-tolerated therapies that achieve durable responses are needed in 3L or earlier to improve CP-CML prognosis.