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Toxicities associated with TKI maintenance therapy following allo-HSCT in patients with Ph+ ALL
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A retrospective analysis assessed the toxicities associated with TKI maintenance therapy following allo-HSCT in 185 adult patients with Ph+ ALL.1 Patients were divided into three groups based on the first TKI they received post-allo-HSCT: imatinib (n = 50), 2G-TKI (n = 118), or ponatinib (n = 17). Results from this analysis were published in the American Journal of Hematology by Othman et al.1
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TKI maintenance therapy post-allo-HSCT in patients with Ph+ ALL was associated with significant toxicities, which lead to dose reductions, interruptions, and discontinuations in 41.6%, 65.4%, and 35.7% of patients, respectively. |
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The most common toxicities leading to TKI discontinuation included gastrointestinal intolerance (16.0%), cytopenias (6.0%), and fluid retention (6.0%). |
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Ponatinib was associated with lower dose interruptions (47.1% vs 54.0% vs 72.9%; p = 0.01) and discontinuations (17.1% vs 38.0% vs 51.7%; p = 0.02) vs imatinib and 2G-TKIs, respectively. Ponatinib was also associated with a longer duration of maintenance therapy vs 2G-TKIs (576.0 days vs 254.5 days; p = 0.02). |
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The 5-year OS and PFS rates for the total population were 79% and 71%, respectively, with no differences based on TKI selection. |
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These findings highlight the significant toxicities associated with TKI maintenance therapy post-allo-HSCT in patients with Ph+ ALL. TKIs with fewer toxicities, such as ponatinib, or other novel therapies may improve outcomes for this patient population. |
Abbreviations: 2G, second-generation; ALL, acute lymphoblastic leukemia; allo-HSCT, allogeneic hematopoietic stem cell transplantation; OS, overall survival; PFS, progression-free survival; Ph+, Philadelphia-positive; TKI, tyrosine kinase inhibitor.
- Othman T, Koller, P, Tsai NC, et al. Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia. Am J Hematol. 2024;99(9):1680-1690 DOI: 10.1002/ajh.27378
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