Phase 3 study of gilteritinib versus salvage chemotherapy in predominantly Asian patients with relapsed/refractory FLT3-mutated acute myeloid leukemia
The phase 3 COMMODORE trial evaluated gilteritinib versus salvage chemotherapy (SC) in a predominantly Asian relapsed/refractory (R/R) FLT3-mutated (FLT3<sup>mut+</sup>) 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 FLT3<sup>mut+</sup> AML.
Authors
- Ligen Liu (ORCID: https://orcid.org/0000-0002-3971-783X)
- Larisa Girshova (ORCID: https://orcid.org/0000-0002-0559-9556)
- Bin Jiang (ORCID: https://orcid.org/0000-0003-2473-2129)
- Nahla Hasabou
- Masanori Kosako (ORCID: https://orcid.org/0000-0002-4981-9450)
- Masato Takeuchi (ORCID: https://orcid.org/0000-0002-2990-2687)
- Elena Martynova (ORCID: https://orcid.org/0000-0003-0802-0236)
- Jianda Hu (ORCID: https://orcid.org/0000-0002-4438-2544)
- Taishi Sakatani (ORCID: https://orcid.org/0000-0001-9585-3855)
- Takeshi Kadokura
- Lily Wong Lee Lee
- Jianxiang Wang (ORCID: https://orcid.org/0000-0001-9437-9151)
- Sergey N. Bondarenko (ORCID: https://orcid.org/0000-0002-2446-8092)
- Jian Li (ORCID: https://orcid.org/0000-0002-4549-0694)
- Hao Jiang (ORCID: https://orcid.org/0000-0003-4123-4930)
- Xin Du (ORCID: https://orcid.org/0000-0003-2648-9433)
- Archrob Khuhapinant
- Menghe Yuan
- Jerome Tan
- Xiao Ma (ORCID: https://orcid.org/0009-0000-3912-5351)
Institutions
- Fujian Medical University (CN)
- Siriraj Hospital (TH)
- Astellas Pharma (Japan) (JP)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Mahidol University (TH)
- Peking Union Medical College Hospital (CN)
- Federal Almazov North-West Medical Research Centre (RU)
- Astellas Pharma (China) (CN)
- Tongren Hospital (CN)
- Krasnoyarsk Regional Clinical Hospital (RU)
- Peking University People's Hospital (CN)
- Peking University International Hospital (CN)
- Institute of Hematology & Blood Diseases Hospital (CN)
- Guangdong Provincial People's Hospital (CN)
- KPJ Ampang Puteri Specialist Hospital (MY)
- Union Hospital (CN)
- Queen Elizabeth Hospital (MY)
- Astellas Pharma (United States) (US)
- Saint Petersburg State Pediatric Medical University (RU)
Publication Details
- Journal
- Leukemia
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1038/s41375-024-02382-9
- Citations
- 11
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 5.00
Funders
- Astellas Pharma US
- Astellas Pharma