Response rate and Survival of patients with Chronic Phase-Chronic Myeloid Leukemia on Second-line Treatment in Tanzania

1. Tanzanian CML patients are younger and present with high disease burden that confer molecular resistance to the first-line imatinib therapy 2. Second-generation TKIs yield excellent survival in responders, while non-responders have poor outcomes driven by high-risk disease features Since 2019, second and third-generation tyrosine kinase inhibitors have been available in Tanzania through the Max Foundation’s drug access program for chronic myeloid leukemia (CML) patients with poor responses to imatinib. This study evaluated treatment response and survival among patients switched to second-line TKIs between January 2019 and January 2025. Clinical and laboratory data were collected at scheduled visits, with complete hematologic response (CHR) assessed routinely and BCR::ABL1 transcript levels monitored after ≥12 months. Molecular responses were categorized as BCR::ABL1 ≤10%, ≤1%, and ≤0.1% (International Scale). A total of 111 patients (median age 40 years; 51.3% male) switched therapy, most in chronic phase (81.9%) and high-risk sokal group (63.6%). Median imatinib exposure before switching was 30 months; main reasons were molecular resistance (68.5%), hematologic resistance (19.8%), and intolerance (11.7%). By 24 months, CHR, BCR::ABL1 ≤10%, ≤1%, and ≤0.1% were achieved in 82.6%, 53.5%, 40.9%, and 33% of CP-CML patients, respectively, with BCR::ABL1 ≤1% strongly predicting 5-year overall survival (OS). During follow-up, 41.8% required third-line and 9.1% fourth-line therapy; 18 patients progressed to blast crisis and 17 died. Five-year OS for the entire cohort was 72.7%. Survival differed according to molecular response with 5-year OS of 93.6% for patients achieving BCR::ABL1 ≤10%, 95.7% for BCR::ABL1 ≤1%, 94.4% for BCR::ABL1 ≤0.1%, compared with 48.0% among those with BCR::ABL1 >10%. Second-line TKIs are effective in Tanzanian CP-CML patients after imatinib failure, with excellent survival in responders but poor outcomes in non-responders, underscoring the need for early detection of resistance and timely treatment optimization.