Pb2426: sorafenib maintenance tailored to flt3-mutated aml after allogeneic hct is highly feasible and effective: a real-life experience

Topic: 22. Stem cell transplantation - Clinical Background: Acute myeloid leukemia (AML) with mutation of the FMS-like tyrosine kinase 3 gene (FLT3) remains to this day one of the greatest challenges of modern haematology, due to poor prognosis despite allogeneic hematopoietic stem cell transplantation (HCT). FLT3 inhibitors - such as the multi-targeted tyrosine kinase inhibitor sorafenib - have proved their efficacy in both induction and salvage treatment. The use of sorafenib in maintenance after HCT is part of the ALWP (acute leukemia working party) - EBMT (European Society for Blood and Marrow Transplantation) recommendation to optimize long-term disease control. Of note, the use of FLT3-inhibitors in maintenance after HCT is off-label, although sorafenib proved to be safe and efficient in significantly reducing cumulative incidence of relapse and improving survival. Aims: The aim of our study is to evaluate the safety and efficacy in preventing early and late relapse in AML-FLT3+ after HCT. Methods: We hereby report data from 20 adult patients with FLT3-ITD+ AML receiving sorafenib after HCT between Feb-2017 and Feb-2023 (patients features are reported in table 1). Sorafenib was given off-label after provision of an informed signed consent. Fourteen patients in complete remission (CR) after HCT received sorafenib as a maintenance treatment for high-risk disease; 5 patients received sorafenib due to molecular relapse, while 1 patient was given sorafenib as a salvage therapy for hematologic relapse after HCT. Of note, 14 patients received FLT3 inhibitors prior to transplant (in association with first line chemotherapy or as salvage therapy). Results: The median time of initiation of sorafenib from HCT was 118 days (49-904). The median follow-up is 1414 days (180-2252) and the median treatment duration was 698 days (3-1431). Nine patients are currently under treatment - median treatment duration 405 days (80-1382). Sorafenib was introduced at minimum dosage of 200 mg daily, to reduce the drug-drug-interaction with concomitant therapies. Six patients required a reduction to 200 mg every-other-day to mitigate the gastro-intestinal discomfort. One patient was able to increment the dosage up to the maximum dosage of 400 mg twice daily without toxicities as well. Sorafenib was overall well-tolerated, with only 2 patients discontinuing it for grade 3 – CTC AE toxicity (one gastro-intestinal toxicity and one cardiac toxicity). Two patients discontinued sorafenib due to disease progression (1 patient after 860 days, and was rescued with a second HCT; 1 patient after 200 days, and died from overt relapse). Eight patients completed the 2-years maintenance with sorafenib – median time of treatment 965 days (651 - 1431). All but one maintained a persistent long-lasting response – median follow-up from discontinuation 634 days (480 - 1280). A single patient restarted sorafenib due to early re-appearance of MRD+ in two subsequent controls: after resumption of sorafenib, MRD negativity was achieved soon after and he is still in CR. Overall, 16/18 patients with FLT3-ITD+ AML achieved stable long-lasting CR, with none of them experiencing major long-term toxicity. Summary/Conclusion: Our real-life practice confirms that sorafenib maintenance therapy is well-tolerated and contributes to sustained long-lasting remissions of FLT3+ AML after allogeneic HCT. Sorafenib should be considered a feasible and effective therapeutic option as maintenance drug in this post-transplant context.Keywords: flt3 inhibitor, Allogeneic hematopoietic stem cell transplant, Acute myeloid leukemia, FLT3