EBMT 2021 | TKI maintenance after SCT in FLT3-ITD positive AML
Nico Gagelmann, MD, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, outlines the findings of a meta-analysis investigating tyrosine kinase inhibitor (TKI) maintenance therapy after stem cell transplantation (SCT) for patients with FLT3-ITD positive acute myeloid leukemia (AML). Seven studies were included in the analysis, five of which evaluated sorafenib, and two of which evaluated midostaurin. The study found that post-transplant maintenance with TKIs was associated with improved outcomes in relapse and survival. This interview took place during the 47th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2021.
Transcript (edited for clarity)
Our main goal was to elaborate a bit more on the effects of TKI maintenance after stem cell transplantation, and FLT3 ITD mutated acute myeloid leukemia. There was aggregating evidence during the last two years with prospective studies and smaller retrospective studies, with the potential benefit of TKI maintenance after stem cell transplantation. But in stem cell transplantation, there is a lack of evidence creation...
Our main goal was to elaborate a bit more on the effects of TKI maintenance after stem cell transplantation, and FLT3 ITD mutated acute myeloid leukemia. There was aggregating evidence during the last two years with prospective studies and smaller retrospective studies, with the potential benefit of TKI maintenance after stem cell transplantation. But in stem cell transplantation, there is a lack of evidence creation. So, we have many, many retrospective studies and small prospective studies. And if we have the luxury to get two prospective studies, which were just published over the last year for TKI maintenance, especially sorafenib in FLT3 ITD AML, and a newly prospective study of midostaurin for TKI maintenance in FLT3 ITD AML, and smaller retrospective studies.
So, we wanted to synthesize this evidence and found that TKI maintenance, irrespective of the TKI, so midostaurin or sorafenib, significantly improved the relapse-free survival, the incidence of relapse, and especially the overall survival. What we then found was that there was no particular difference between TKI maintenance and the control group, which was mainly placebo, in non-relapse mortality. But there seemed to be a difference and an increased chronic GvHD and acute GvHD, especially for studies which investigated sorafenib.
These findings underscore the benefit of TKI maintenance for these patients, but also highlight future research opportunities to identify whether, especially sorafenib, for which most evidence exists for its benefit for now, whether sorafenib has potential to create some GVL effect, which would then also be correlated with acute GvHD and chronic GvHD incidences we see, which are increased after sorafenib therapy, or whether this is mainly a difficult differential diagnosis because the main toxic effects of sorafenib were skin toxicity. And this differential diagnosis between skin GvHD and skin toxicity need to be more identified and researched more over the next few months hopefully, or even the few years.
So, we found overall a significant benefit of TKI maintenance, especially for sorafenib, and future prospects for GvHD evaluations, and create the basis for future studies on TKI maintenance and maintenance overall in these patients, patient subgroups in AML.
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