FLT3

EBMT 2018 | The effect of sorafenib on post-transplant outcomes of FLT3-ITD mutated AML patients: a report from a Chinese study

At present, it is not clear whether sorafenib maintenance after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has any significant impact on the survival of fms like tyrosine kinase – internal tandem duplication (FLT3-ITD) mutated acute myeloid leukemia (AML) patients. Li Xuan from the Nanfang Hospital, Guangzhou, China, and colleagues, retrospectively assessed the effect of maintenance therapy with sorafenib, a multi-kinase inhibitor, on the clinical outcomes of FLT3-ITD mutated AML patients undergoing allo-HSCT. The findings of this study were presented at the 44th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Lisbon, Portugal.

Overall, 144 consecutive FLT3-ITD AML patients (median age at the time of transplantation = 35 years, range, 14–57) who underwent allo-HSCT between January 2012–December 2015 were enrolled in this retrospective multicenter study. Sorafenib therapy pre-HSCT was initiated at the time of induction, post-remission maintenance or relapse, and continued until one week prior to the start of the conditioning regimen. Sorafenib maintenance post-HSCT was started from day 30 to 180 post-transplantation. Either before or after transplantation, the initial dose of sorafenib was 400 mg twice daily and was adjusted on the basis of suspected toxicity or emerging drug resistance (dose range, 200-800 mg daily).

Depending on whether they were receiving sorafenib before transplantation or sorafenib maintenance after transplantation, patients were divided into four groups including patients receiving sorafenib before transplantation (Group A, n = 36), patients receiving sorafenib maintenance after transplantation (Group B, n = 32), patients receiving sorafenib both before and after transplantation (Group C, n = 26), and patients receiving sorafenib neither before nor after transplantation (Group D, n = 50).

Key findings:
  • Relapse
    • Median follow-up: 142 days (range, 44–589) post-transplantation
    • 3-year relapse rates in group A, B, C, and D were 22.2% ± 8.3%, 18.8% ± 3.1%, 15.8% ± 3.8% and 46.1 ± 19.1% respectively, P = 0.0006
    • Significant protective factors for lower relapse include sorafenib pre-transplantation (HR = 0.436, P = 0.048), sorafenib maintenance post-transplantation (HR = 0.431, P = 0.046) and combined application (HR = 0.173, P = 0.002)
  • Survival
    • Median follow-up: 707 days (range, 38–1959) post-transplantation
    • 3-year overall survival (OS) in group A, B, C, and D were 74.9% ± 7.2%, 78.1% ± 7.3%, 84.6% ± 7.1% and 50.9% ± 7.6% respectively, P = 0.023
    • 3-year leukemia free survival (LFS) in group A, B, C, and D were 69.4% ± 7.7%, 78.1% ± 7.3%, 80.4% ± 7.9% and 34.8% ± 7.0% respectively, P < 0.001
    • Significant protective factors for longer LFS include sorafenib pre-transplantation (HR = 0.322, P = 0.010), sorafenib maintenance post-transplantation (HR = 0.343, P = 0.014) and combined application (HR = 0.187, P = 0.001)
  • Most common side effect was skin rash which reduced gradually after reduction/discontinuation of sorafenib or in combination with glucocorticoid

The authors concluded by stating that “sorafenib before transplantation, sorafenib maintenance after transplantation, and their combined application all could improve the outcomes for patients with FLT3-ITD AML. Further study is needed to determine whether the use of sorafenib both before and after transplantation might be ideal”. Currently, there is an ongoing multicenter randomized study (NCT02474290), which is evaluating the efficacy of sorafenib for prophylaxis of leukemia relapse in FLT3-ITD AML patients undergoing allo-HSCT.

The results of this study were recently published in the March 2018 issue of Cancer.

References
  1. Xuan L. et al. The effect of sorafenib on the outcomes of acute myeloid leukemia with FLT3-ITD undergoing allogeneic hematopoietic stem cell transplantation. Oral abstract #OS7-2. 2018 European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, Lisbon, PT.
  2. Xuan L. et al. Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation. Cancer. 2018 Mar 6. DOI: 10.1002/cncr.31295. [Epub ahead of print].
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