Outcomes with sequential FLT3-inhibitor-based therapies in patients with AML

Journal of Hematology & Oncology

Rashmi Kanagal-Shamanna¹  Keyur P. Patel¹  Sanam Loghavi¹  Mansour Alfayez²  Jorge E. Cortes²  Marina Y. Konopleva²  Naval G. Daver²  Naveen Pemmaraju²  Maro Ohanian²  Michael Andreeff²  Sherry A. Pierce²  Koichi Takahashi²  Nicholas J. Short²  Guillermo Montalban-Bravo²  Hagop M. Kantarjian²  Musa Yilmaz²  Gautam Borthakur²  Guillermo Garcia-Manero²  Ahmad S. Alotaibi²  Tapan M. Kadia²  Rita Assi²  Courtney D. DiNardo²  Elias J. Jabbour²  Farhad Ravandi²  Issa Ghayas² 

[1] Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit FC4.2012, 77030, Houston, TX, USA;

关键词: FLT3 mutations;    Sequential FLT3 inhibitors;    Midostaurin;    Sorafenib;    Quizartinib;    Gilteritinib;    FLT3-PCR;    Low-intensity therapy;   

DOI  :  10.1186/s13045-020-00964-5

来源: Springer

【 摘 要 】

BackgroundSecond-generation FLT3-inhibitors (FLT3i) demonstrated single-agent composite CR rates (CRc) of 45–55% in patients with relapsed/refractory (R/R) FLT3-mutated AML in phase II/III trials. However, > 85% of patients treated were prior FLT3i naïve. The response rates to sequential FLT3i exposure remain poorly defined.MethodsWe retrospectively reviewed patients with FLT3-mutated AML between November 2006 and December 2019.ResultsIn frontline patients treated with a FLT3i (cohort 1), the CRc rates and median overall survival (OS) with the first (n = 56), second (n = 32), and third FLT3i-based (n = 8) therapy were 77%, 31%, and 25%, and 16.7 months, 6.0 months, and 1.4 months, respectively. In patients receiving a FLT3i-based therapy for the first time in a R/R AML setting (cohort 2), the CRc rates and median OS were 45%, 21%, and 10%, and 7.9 months, 4.0 months, and 4.1 months with the first (n = 183), second (n = 89), and third/fourth (n = 29) FLT3i-based therapy, respectively.In cohort 1, CRc rates with single-agent FLT3i (n = 21) versus FLT3i-based combinations (n = 19) in second/third sequential FLT3i exposures were 19% versus 42%, respectively. In cohort 2, the CRc rates with single-agent FLT3i (n = 82) versus FLT3i-based combinations (n = 101) in first FLT3i exposure were 34% versus 53%, respectively, and those with single-agent FLT3i (n = 63) versus FLT3i-based combinations (n = 55) in second/third/fourth sequential FLT3i exposures were 13% versus 25%, respectively.ConclusionCRc rates drop progressively with sequential exposure to FLT3i’s in FLT3-mutated AML. In all settings, CRc rates were higher with FLT3i-based combinations compared with single-agent FLT3i therapy in similar FLT3i exposure settings.

【 授权许可】

CC BY