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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1136-1141
Number of pages6
JournalAmerican Journal of Hematology
Volume93
Issue number9
DOIs
StatePublished - Sep 2018
Externally publishedYes

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Azacitidine
Acute Myeloid Leukemia
sorafenib
Stem Cells
Clinical Trials
Transplants
Drug Therapy
Survival
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Ohanian, M., Garcia-Manero, G., Levis, M., Jabbour, E., Daver, N., Borthakur, G., ... Ravandi, F. (2018). Sorafenib Combined with 5-azacytidine in Older Patients with Untreated FLT3-ITD Mutated Acute Myeloid Leukemia. American Journal of Hematology, 93(9), 1136-1141. https://doi.org/10.1002/ajh.25198

Sorafenib Combined with 5-azacytidine in Older Patients with Untreated FLT3-ITD Mutated Acute Myeloid Leukemia. / Ohanian, Maro; Garcia-Manero, Guillermo; Levis, Mark; Jabbour, Elias; Daver, Naval; Borthakur, Gautam; Kadia, Tapan; Pierce, Sherry; Burger, Jan; Richie, Mary Ann; Patel, Keyur; Andreeff, Michael; Estrov, Zeev; Cortes, Jorge; Kantarjian, Hagop; Ravandi, Farhad.

In: American Journal of Hematology, Vol. 93, No. 9, 09.2018, p. 1136-1141.

Research output: Contribution to journalArticle

Ohanian, M, Garcia-Manero, G, Levis, M, Jabbour, E, Daver, N, Borthakur, G, Kadia, T, Pierce, S, Burger, J, Richie, MA, Patel, K, Andreeff, M, Estrov, Z, Cortes, J, Kantarjian, H & Ravandi, F 2018, 'Sorafenib Combined with 5-azacytidine in Older Patients with Untreated FLT3-ITD Mutated Acute Myeloid Leukemia', American Journal of Hematology, vol. 93, no. 9, pp. 1136-1141. https://doi.org/10.1002/ajh.25198
Ohanian, Maro ; Garcia-Manero, Guillermo ; Levis, Mark ; Jabbour, Elias ; Daver, Naval ; Borthakur, Gautam ; Kadia, Tapan ; Pierce, Sherry ; Burger, Jan ; Richie, Mary Ann ; Patel, Keyur ; Andreeff, Michael ; Estrov, Zeev ; Cortes, Jorge ; Kantarjian, Hagop ; Ravandi, Farhad. / Sorafenib Combined with 5-azacytidine in Older Patients with Untreated FLT3-ITD Mutated Acute Myeloid Leukemia. In: American Journal of Hematology. 2018 ; Vol. 93, No. 9. pp. 1136-1141.
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AU - Daver, Naval

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