Phase 3 study of gilteritinib versus salvage chemotherapy in predominantly Asian patients with relapsed/refractory FLT3-mutated acute myeloid leukemia

Wang J 1 , Jiang B 2 , Li J 3 , Liu L 4 , Du X 5 , Jiang H 6 Show all authors , Hu J 7 , Yuan M 8 , Sakatani T 9 , Kadokura T 9 , Takeuchi M 9 , Kosako M 9 , Ma X 8 , Girshova L 10 , Tan J 11 , Bondarenko S 12 , Lee LWL 13 , Khuhapinant A 14 , Martynova E 15 , Hasabou N 16

Affiliations 

  • 1 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. wangjx@ihcams.ac.cn
  • 2 Department of Hematology, Peking University International Hospital, Beijing, China
  • 3 Department of Hematology, Peking Union Medical College Hospital, Beijing, China
  • 4 Department of Hematology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 5 Department of Hematology, Guangdong Provincial People's Hospital, Guangzhou, China
  • 6 Department of Hematology, Peking University People's Hospital, Beijing, China
  • 7 Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
  • 8 Astellas China Investment Co, Ltd., Beijing, China
  • 9 Astellas Pharma, Inc., Tokyo, Japan
  • 10 Almazov National Medical Research Centre, St. Petersburg, Russia
  • 11 Department of Hematology, Ampang Hospital, Selangor, Malaysia
  • 12 Clinical Research Institution of Pediatric Hematology and Transplantation Under the Name of Raisa Gorbacheva, State Medical University, St. Petersburg, Russia
  • 13 Department of Hematology, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia
  • 14 Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • 15 Krasnoyarsk Regional Clinical Hospital, Krasnoyarsk, Russia
  • 16 Astellas Pharma, Inc., Northbrook, IL, USA
Leukemia, 2024 Sep 05.
PMID: 39237634 DOI: 10.1038/s41375-024-02382-9

Abstract

The phase 3 COMMODORE trial evaluated gilteritinib versus salvage chemotherapy (SC) in a predominantly Asian relapsed/refractory (R/R) FLT3-mutated (FLT3mut+) acute myeloid leukemia (AML) patient population. The primary endpoint was overall survival (OS); secondary endpoints included event-free survival (EFS) and complete remission (CR) rate. As of June 30, 2020 (interim analysis: 32.2 months after study initiation), 234 patients were randomized (gilteritinib, n = 116; SC, n = 118). Median OS was significantly longer with gilteritinib versus SC (9.6 vs. 5.0 months; HR 0.566 [95% CI: 0.392, 0.818]; p = 0.00211) with a median follow-up of 10.3 months. Median EFS was also significantly longer with gilteritinib (2.8 vs. 0.6 months; HR 0.551 [95% CI: 0.395, 0.769]; p = 0.00004). CR rates with gilteritinib and SC were 16.4% and 10.2%, respectively; composite CR rates were 50.0% and 20.3%, respectively. Exposure-adjusted grade ≥3 adverse event (AE) rates were lower with gilteritinib (58.38 events/patient-year [E/PY]) versus SC (168.30 E/PY). Common AEs with gilteritinib were anemia (77.9%) and thrombocytopenia (45.1%). Gilteritinib plasma concentration peaked ~4 h postdose; ~3-fold accumulation occurred with multiple dosing. The COMMODORE trial demonstrated that gilteritinib significantly improved OS and EFS in predominantly Asian patients, validating the outcomes of gilteritinib from the ADMIRAL trial in R/R FLT3mut+ AML.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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