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Annals of Hematology

, Volume 94, Issue 11, pp 1899–1905 | Cite as

Synergistic effect of sorafenib and cGvHD in patients with high-risk FLT3-ITD+AML allows long-term disease control after allogeneic transplantation

  • A. Tschan-Plessl
  • J. P. Halter
  • D. Heim
  • M. Medinger
  • J. R. Passweg
  • S. Gerull
Original Article

Abstract

The multikinase inhibitor sorafenib has shown a strong anti-leukemic effect in FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML); however, remission is often transient. To better understand the role of sorafenib, we performed a retrospective analysis of all patients who received sorafenib in combination with allogeneic hematopoietic stem cell transplantation (HSCT) at our center. Seventeen patients with FLT3-ITD positive AML were treated with sorafenib in combination with allogeneic HSCT. Seven patients received sorafenib therapy pre- and posttransplant, and 10 patients were given sorafenib only posttransplant. Median duration of sorafenib treatment was 13 months (range 1–42); median dose was 600 mg (range 100–1200). Fourteen patients (82 %) achieved a complete remission (CR), while 5 patients (29 %) eventually developed progressive disease. Developing chronic graft-versus-host disease (GvHD) had a strong protective influence on the risk of sorafenib resistance (p = 0.028, HR 0.08, 95 % CI 0.01–0.76). In a total of 8 patients, sorafenib had to be stopped, paused or dose-reduced due to toxicity. In 5 patients with pronounced toxicity, we switched to an alternating dosing schedule with 1 month on/1 month off sorafenib. These patients subsequently remained in sustained complete molecular remission, with a median follow-up of 20 months. Our data indicate that sorafenib can achieve high rates of sustained remission in high-risk patients treated in combination with HSCT.

Keywords

flt3 Tyrosine-kinase inhibitor Sorafenib Allogeneic 

Notes

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • A. Tschan-Plessl
    • 1
  • J. P. Halter
    • 1
  • D. Heim
    • 1
  • M. Medinger
    • 1
  • J. R. Passweg
    • 1
  • S. Gerull
    • 1
  1. 1.Department of HematologyUniversity Hospital BaselBaselSwitzerland

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