Third-line TKI Increases Non-relapse Mortality After Allo-HSCT in CML

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Multiple lines of TKI therapy are associated with higher NRM rates among patients with chronic myelogenous leukemia who undergo allo-HSCT.
Multiple lines of TKI therapy are associated with higher NRM rates among patients with chronic myelogenous leukemia who undergo allo-HSCT.

Multiple lines of tyrosine kinase inhibitor (TKI) therapy are associated with higher rates of non-relapse mortality (NRM) among patients with chronic myelogenous leukemia (CML) who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT), according to a study published in the American Journal of Hematology.1

Allo-HSCT is reserved for patients with CML whose disease progresses after multiple lines of TKI treatment. The aim of this study was to determine if TKI use prior to allo-HSCT affects outcomes.

The study included 237 patients diagnosed with chronic phase CML who were treated with at least 1 TKI and underwent allo-HSCT. The median age was 42 and 153 patients received 1 TKI, 49 received 2 TKIs, and 35 received 3 TKIs.

The 2-year overall survival (OS) for the entire cohort was 63.7% (95% CI, 57.0-69.7%) and leukemia-free survival (LFS) was 57.0% (95% CI, 50.2-63.1%).

Patients who received 3 lines of TKI therapy demonstrated significantly shorter 2-year OS (53.9%) and LFS (46.1%) compared with patients who received 1 or 2 lines of TKI treatment (OS, 66.7%; P = .020; and LFS, 60.7%; P = .027).

There was no significant difference in OS or LFS among patients who received 1 or 2 prior TKIs.

The OS difference was driven by higher NRM. The 2-year NRM was 17% with 1 to 2 prior TKIs compared with 33.8% with 3 prior TKIs (P = .005). Relapse incidence was similar between the 1/2 and 3 prior TKI groups (24.0 vs 20.1%; P = .840).

OS and LFS were also negatively affected by HLA disparities, advanced disease stage at transplantation, and patient age 50 or older after multivariate analysis.

RELATED: BCR-ABL1 Transcript Type Predicts Outcomes After Imatinib in CML

These data suggest that 3 lines of TKI therapy are a risk factor for mortality after allo-HSCT. According to the authors, “allo-HSCT could be considered for young patients with CML showing resistance to second-line TKI therapy.”

Reference

  1. Kondo T, Nagamura-Inoue T, Tojo A, et al. Clinical impact of pre-transplant use of multiple tyrosine kinase inhibitors on the outcome of all-HSCT for CML. Am J Hematol. 2017 May 22. doi: 10.1002/ajh.24793 [Epub ahead of print]

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