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Impact of induction regimen and allo-HSCT on survival outcomes in patients with Ph+ ALL
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A multi-institutional, real-world, retrospective analysis conducted through the COMMAND assessed the outcomes of patients with Ph+ ALL.1 This analysis included 431 adult patients diagnosed between May 2003 and December 2022, who received treatment with either IC (n = 317) or NIC (n = 112) first-line TKI-based regimens, with or without allo-HSCT.1 Results from this analysis were published in the American Journal of Hematology by Badar, et al.1 |
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The study demonstrated that, in comparison to first-generation TKIs, second- and third-generation TKIs improved RFS and OS in patients with Ph+ ALL. The 3-year RFS rates with second- and third-generation TKIs were 66% compared to 47.5% with first-generation TKIs (HR, 0.76; p = 0.087), while the 3-year OS rates were 71.1% vs 55.7%, respectively (HR, 0.66; p = 0.026). |
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IC + TKI regimens were associated with improved long-term survival outcomes than NIC + TKI; median RFS was 129 months vs 36.93 months for IC + TKI and NIC + TKI, respectively (p = 0.003), and median OS was 123.1 months vs 49.40 months, respectively (p = 0.01). |
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In the multivariable analysis, allo-HSCT improved RFS vs no allo-HSCT, regardless of whether patients achieved CMR at 3 months (HR, 0.32; p < 0.001) or did not achieve CMR (HR, 0.22; p <0.001). This benefit remained significant after a baseline time point of 180 days following diagnosis (HR, 0.39; p < 0.001) and 180 days post-allo-HSCT in a propensity-score-matched cohort (HR, 0.37; p < 0.001). |
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Allo-HSCT did not improve OS based on achieving CMR at 3 months (HR, 0.87; p = 0.59) or not achieving CMR (HR, 0.48; p = 0.11). |
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Similarly, OS showed no improvement when assessed after a baseline timepoint of 180 days following diagnosis (HR, 0.75; p = 0.09) and post 180 days of allo-HSCT in a propensity-score-matched cohort (HR, 0.57; p = 0.06); however, in the multivariable analysis using propensity match score, allo-HSCT improved OS (HR, 0.53; p = 0.04). |
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The findings suggest that treatment strategies incorporating newer-generation TKIs and judicious use of allo-HSCT may improve outcomes in patients with Ph+ ALL; however, further studies are needed to refine the selection criteria for allo-HSCT candidates. |
Abbreviations: ALL, acute lymphoblastic leukemia; allo-HSCT, allogeneic hematopoietic stem cell transplantation; CMR, complete molecular remission; COMMAND, Consortium on Myeloid Malignancies and Neoplastic Diseases; HR, hazard ratio; IC, intensive chemotherapy; NIC, non-intensive chemotherapy; OS, overall survival; Ph+, Philadelphia-positive; RFS, relapse-free survival; TKI, tyrosine kinase inhibitor.
- Badar T, Narra R, Mims AS, et al. Impact of induction regimens intensity and allogeneic stem cell transplantation on survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A multi-institutional study. Am J Hematol. 2024. Online ahead of print. DOI: 10.1002/ajh.27475
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