Real-world experience with second and third generation tyrosine kinase inhibitors in imatinib-resistant Nigerian patients with BCR::ABL1 positive chronic myeloid leukaemia.

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Background: Imatinib significantly advances CML management, inducing deep molecular response and increasing survival. However, about one-third of patients develop resistance, often leading to treatment failure and disease progression. For resistant cases, assessing compliance and mutational analysis are crucial. Second-, third-, and fourth-generation TKIs offer alternative options, especially for those with BCR::ABL1 mutations. This study examines the responses and survival of Nigerian patients with CML resistant to imatinib treated with these newer TKIs. Methods: This retrospective descriptive analysis involved 118 BCR::ABL1-positive patients with CML who were resistant to imatinib with BCR::ABL1 mRNA levels ≥0.1% IS after at least 18 months on imatinib, treated from 2014 to 2024. Response to the second generation (2GN) and third generation (3GN) was assessed according to combined NCCN, ESMO, and ELN guidelines, and survival analysis for each group was performed using the Kaplan-Meier survival curve. Results: After a median follow-up of 37.0 (2.3-123.3) months, the dasatinib cohort achieved major molecular remission (MMR) and overall survival (OS) rates of 57.1% and 74.6%, compared to 51.7% and 69.0% in the Nilotinib group, with a median survival of 26.4 (3.3-114.5) months. Moreover, the Bosutinib and Ponatinib groups, after a median follow-up of 33.8 (3.1-81.7) months and 11.2 (1.0-37.9) months, respectively, had MMR rates of 52.6% and 42.9%, and OS rates of 63.2% and 57.1%, respectively. Conclusions: This study showed that dasatinib achieved the highest MMR (57.1%) and OS (74.6%) rates, outperforming nilotinib, bosutinib, and ponatinib.