FLT3,   General AML

Sorafenib as a maintenance agent after allogenic HSCT for FLT3 mutated AML

Fms-Like Tyrosine Kinase 3 (FLT3) positive Acute Myeloid Leukemia (AML) is associated with poor prognosis in patients. Sorafenib, a multi-target tyrosine kinase inhibitor, has shown encouraging results in FLT3 mutated patients, however its role after allogenic Hematopoietic Stem Cell Transplantation (HSCT) is not very clear.

Giorgia Battipaglia from Hôpital Saint-Antoine, Paris, France and colleagues retrospectively studied the outcomes of FLT3 mutated AML patients who received sorafenib after HSCT as a maintenance therapy. The results of the study were published in Cancer.

In total, twenty-seven FLT3 positive AML patients (median age = 46 years) undergoing HSCT received sorafenib maintenance after HSCT at three hematologic departments including Hôpital Saint-Antoine, University of Beirut and King Faisal Specialist Hospital and Research Center.

The key results of the study were:
  • Grade 1–2 toxicities occurred in eleven patients which were reversible
  • Dose reduction and drug withdrawal due to toxicity occurred in four patients respectively
  • Chronic Graft versus Host Disease (GvHD) occurred in thirteen patients (limited [n = 9) and extensive [n = 4])
  • 1-year Progression Free Survival (PFS) and Overall survival in all patients were 92%±5% and 92%±6% respectively

Overall, the authors concluded that sorafenib maintenance after HSCT was “feasible and highly effective with an acceptable toxicity profile” in patients with FLT3 positive AML.

Abstract

BACKGROUND: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results.

METHODS: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia.

RESULTS: The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively.

CONCLUSIONS: Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT.

References
  1. Battipaglia G. et al. Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia. Cancer. 2017 Apr 7. DOI: 10.1002/cncr.30680.