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Clinical Trial
. 2018 Sep;93(9):1136-1141.
doi: 10.1002/ajh.25198. Epub 2018 Aug 31.

Sorafenib Combined with 5-azacytidine in Older Patients with Untreated FLT3-ITD Mutated Acute Myeloid Leukemia

Maro Ohanian  1 , Guillermo Garcia-Manero  1 , Mark Levis  2 , Elias Jabbour  1 , Naval Daver  1 , Gautam Borthakur  1 , Tapan Kadia  1 , Sherry Pierce  1 , Jan Burger  1 , Mary Ann Richie  1 , Keyur Patel  1 , Michael Andreeff  1 , Zeev Estrov  1 , Jorge Cortes  1 , Hagop Kantarjian  1 , Farhad Ravandi  1
Affiliations
Clinical Trial

Sorafenib Combined with 5-azacytidine in Older Patients with Untreated FLT3-ITD Mutated Acute Myeloid Leukemia

Maro Ohanian et al. Am J Hematol. 2018 Sep.

Abstract

Based on our previous study of the combination of sorafenib with 5-azacytidine (AZA) in relapsed/refractory patients with FLT3 mutated acute myeloid leukemia (AML), we hypothesized that the combination would be efficacious and well tolerated in untreated patients with FLT3 mutated AML who are unsuitable for standard chemotherapy due to advanced age or lack of fitness. Newly diagnosed patients with untreated FLT3 mutated AML who underwent frontline therapy on 2 separate protocols of AZA plus sorafenib were analyzed. The clinical trials were registered at clinicaltrials.gov (NCT02196857 and NCT01254890). Overall, 27 patients with untreated FLT3 mutated AML (median age of 74 years, range, 61-86) were enrolled. The overall response rate was 78% (7 [26%] CR, 12 [44%] CRi/CRp, and 2 [7%] PR). Patients received a median of 3 treatment cycles (1-35). The median duration of CR/CRp/CRi is 14.5 months (1.1-28.7 months). Three (11%) responding patients (1 CR, 2 CRi) proceeded to allogeneic stem cell transplant. The median follow-up for surviving patients was 4.1 months (3.0-17.3 months). The median overall survival for the entire group was 8.3 months, and 9.2 months in the 19 responders. The regimen was well tolerated in elderly patients with untreated FLT3 mutated AML with no early deaths.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest with the contents of this article.

Figures

FIGURE 1
FIGURE 1
A, The median OS for the entire group was 8.3 months, and 9.2 months in the 19 responders. B, The median OS in responders was significantly longer than for non-responders [Color figure can be viewed at wieyonlinelibrary.com]
FIGURE 2
FIGURE 2
A, The median remission duration for the responding patients treated with AZA plus sorafenib (soraf) was 14.5 months (1.1–28.7). B, The median relapse-free survival, which censored for loss of response/relapse and death in CR, was 7.1 months (1–29) [Color figure can be viewed at wieyonlinelibrary.com]
FIGURE 3
FIGURE 3
Summary of AEs reported during the clinical trial of AZA plus sorafenib. The majority of AEs were grades 1–2 [Color figure can be viewed at wieyonlinelibrary.com]
See this image and copyright information in PMC

References

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