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. 2024 Jun 24:14:1391743.
doi: 10.3389/fonc.2024.1391743. eCollection 2024.

Sorafenib maintenance in FLT3-ITD mutated AML after allogeneic HCT: a real-world, single-center experience

Elisa Diral  1 , Giulia Furnari  1   2 , Alessandro Bruno  1 , Raffaella Greco  1 , Daniela Clerici  1 , Sarah Marktel  1 , Francesca Farina  1 , Sara Mastaglio  1 , Luca Vago  1   2 , Simona Piemontese  1 , Jacopo Peccatori  1 , Consuelo Corti  1 , Massimo Bernardi  1 , Fabio Ciceri  1   2 , Maria Teresa Lupo-Stanghellini  1
Affiliations

Sorafenib maintenance in FLT3-ITD mutated AML after allogeneic HCT: a real-world, single-center experience

Elisa Diral et al. Front Oncol. .

Abstract

Despite allogeneic hematopoietic stem cell transplant (allo-HCT) and the development of novel FLT3 inhibitors in both induction (midostaurin) and in the relapsed/refractory setting (gilteritinib), FLT3-ITD mutated leukemia (FLT3-ITD+ AML) still represents a challenge for modern hematology. Sorafenib is, to this date, the only inhibitor that demonstrated efficacy in improving both progression-free and overall survival as post-HCT maintenance therapy, even if its use in this setting has not been approved so far by regulatory agencies. The aim of our study was to evaluate the feasibility, safety, and efficacy of sorafenib maintenance in preventing early relapse in FLT3-ITD+ AML after HCT in a single-center experience. We analyzed 26 consecutive patients who received post-HCT 2-year maintenance with sorafenib at our center between 2017 and 2023. The median time from HCT to sorafenib start was 130 days, and the median dosage was 200 mg per day. Two (8%) and three (12%) patients discontinued maintenance due to toxicity and disease relapse, respectively. Eight (31%) patients terminated the 2-year maintenance and stopped sorafenib, while 13 patients are still under treatment. Overall, 21/26 patients (81%) are alive and in stable complete remission as outlined by a 2-year disease-free survival of 83.61%. No major long-term toxicity was reported at the last follow-up. Our real-world experience supports the use of sorafenib as a feasible and effective therapeutic option in post-HCT maintenance for FLT3-ITD+ AML.

Keywords: FLT3 ITD; acute myeloid leukemia; allogeneic stem cell transplantation; maintenance; sorafenib.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CS declared a past co-authorship with the author FC to the handling editor.

Figures

Figure 1
Figure 1
Eligibility and follow-up of patients. AML, acute myeloid leukemia; CR, complete remission; GvHD, graft-versus-host disease. A total of 79 patients with FLT3-ITD AML underwent transplantation; of these, 47 patients did not receive sorafenib due to various reasons— GvHD, early relapse, or severe infections; eight patients were lost to follow-up. The study group included 26 patients who received sorafenib; five patients discontinued maintenance for toxicity or relapse, while 21 patients tolerated the treatment well. Of these patients, 13 are still under treatment.
Figure 2
Figure 2
Outcomes: graft-versus-host disease/relapse-free survival (A), overall survival (B), and disease-free survival (C) among patients treated with sorafenib (black line) and patients untreated with sorafenib as post-allo-HCT maintenance (dotted line).
See this image and copyright information in PMC

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