Post-transplant maintenance tyrosine kinase inhibitor (TKI) therapy is feasible and may decrease disease relapses and improve outcomes in patients with high-risk Philadelphia chromosome-positive (Ph+) leukemia following allogeneic hematopoietic cell transplantation (HCT), a study published in Clinical Lymphoma, Myeloma & Leukemia has shown.1
Because the impact of post-transplant maintenance TKIs on outcomes in this treatment setting remain unclear, researchers sought to conduct a retrospective analysis to evaluate maintenance post-transplant therapy with imatinib, dasatinib, nilotinib, or ponatinib.
For the study, researchers analyzed data from 26 allograft recipients with accelerated or blast phase chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) who received post-transplant maintenance TKI therapy with imatinib, dasatinib, nilotinib, or ponatinib between 2004 and 2014.
Particular TKI selection was based on pretransplant TKI response, anticipated toxicities, and the presence of ABL1 domain mutations. Newer generations TKIs (i.e., dasatinib, nilotinib, ponatinib) were initiated at a dose reduction of 50% or more from the standard pretransplant dosing to minimize toxicities and avoid treatment interruption.
Results showed that TKIs were initiated at a median of 100 days following allogeneic HCT and were administered for a median of 16 months. A total of 8 patients discontinued maintenance TKI treatment due to adverse events.
Researchers found that at a median follow-up of 3.6 years, the 5-year relapse-free survival was 61%. The 3 patients who relapsed successfully received salvage therapy and remain disease-free as of this analysis. The 5-year overall survival rate was 78%.
- DeFilipp Z, Langston AA, Chen Z, et al. Does post-transplant maintenance therapy with tyrosine kinase inhibitors improve outcomes of high-risk Philadelphia chromosome-positive leukemia? [published online ahead of print May 5, 2016]. Clin Lymphoma Myeloma Leuk. doi: 10.1016/j.clml.2016.04.017.