BCR::ABL1 kinase domain mutations and their predictive value for treatment outcomes in patients with chronic myeloid leukemia treated with first-line imatinib in a low-income setting: Experience from Côte d'Ivoire.

BACKGROUND

We aimed to analyse the incidence of BCR::ABL1 kinase domain mutations in patients newly diagnosed with or undergoing treatment for chronic myeloid leukemia (CML) in Côte d'Ivoire, as well as to evaluate the predictive factors associated with treatment outcomes.

METHODS

We evaluated 42 patients with suboptimal molecular response who underwent BCR::ABL1 kinase domain mutation screening. Sequencing was performed in collaboration with the Fred Hutchinson Cancer Research Center, Seattle, USA.

RESULTS

Among the 42 patients, 16 (38.1%) were found to have known BCR::ABL1 point mutations. A total of nine distinct mutations were identified, with T315I being the most common (5). Three patients harbored compound mutations: one had T315I + M244V, another had G250E + E459K, and the third had H396P + E459K. The 5-year overall survival (OS) rate was significantly lower in patients with BCR::ABL1 mutations (85%; 95 % CI: 51.0%-96.1%) compared to those without mutations (100%). However, there was no statistically significant difference in OS between patients with T315I mutations (83.3 %; 95 % CI: 27.4%-97.5%) and those without T315I (83.3%; 95% CI: 5.9%-98.8%). Being in the chronic phase of the disease and having a low-risk ELTS score were identified as protective factors against the development of mutations.

CONCLUSION

Our findings support the recommendation for BCR::ABL1 mutation screening in CML patients with an inadequate initial response or evidence of loss of response. Screening is also advised at progression to the accelerated or blast phase, and in patients with high-risk ELTS scores, and mutation profiles may serve as important prognostic indicators.