Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial
Perl, Alexander E. (University of Pennsylvania)
Larson, Richard A (University of Chicago)
Podoltsev, Nikolai A. (Yale School of Medicine)
Strickland, Stephen. (Vanderbilt-Ingram Cancer Center)
Wang, Eunice S. (Roswell Park Comprehensive Cancer Center)
Atallah, Ehab (Cancer Center-Froedtert Hospital)
Schiller, Gary J. (David Geffen School of Medicine at UCLA)
Martinelli, Giovanni (IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori,")
Neubauer, Andreas (Universitätsklinikum Giessen und Marburg GmbH)
Sierra, Jorge (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Montesinos, Pau (Hospital Universitari i Politècnic La Fe (València))
Récher, Christian (Centre Hospitalier Universitaire de Toulouse)
Yoon, Sung Soo (Seoul National University Hospital)
Hosono, Naoko (University of Fukui)
Onozawa, Masahiro (Hokkaido University)
Chiba, Shigeru (University of Tsukuba)
Kim, Hee-Je (Catholic Hematology Hospital)
Hasabou, Nahla (Astellas Pharma US. Inc)
Lu, Qiaoyang (Astellas Pharma US. Inc)
Tiu, Ramon (Astellas Pharma US. Inc)
Levis, Mark (Johns Hopkins University)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2022
Resum:	The phase 3 ADMIRAL (NCT02421939; Study ID: 2215-CL-0301) trial showed superior overall survival in patients with relapsed/refractory FLT3-mutation-positive acute myeloid leukemia (AML) randomized 2:1 to receive the oral FMS-like tyrosine kinase 3 inhibitor gilteritinib vs those randomized to receive salvage chemotherapy (SC). Here we provide a follow-up of the ADMIRAL trial 2 years after the primary analysis to clarify the long-term treatment effects and safety of gilteritinib in these patients with AML. At the time of this analysis, the median survival follow-up was 37. 1 months, with deaths in 203 of 247 and 97 of 124 patients in the gilteritinib and SC arms, respectively; 16 gilteritinib-treated patients remained on treatment. The median overall survival for the gilteritinib and SC arms was 9. 3 and 5. 6 months, respectively (hazard ratio, 0. 665; 95% confidence interval [CI], 0. 518, 0. 853; two-sided P =. 0013); 2-year estimated survival rates were 20. 6% (95% CI, 15. 8, 26. 0) and 14. 2% (95% CI, 8. 3, 21. 6). The gilteritinib-arm 2-year cumulative incidence of relapse after composite complete remission was 75. 7%, with few relapses occurring after 18 months. Overall, 49 of 247 patients in the gilteritinib arm and 14 of 124 patients in the SC arm were alive for ≥2 years. Twenty-six gilteritinib-treated patients remained alive for ≥2 years without relapse; 18 of these patients underwent transplantation (hematopoietic stem cell transplantation [HSCT]) and 16 restarted gilteritinib as post-HSCT maintenance therapy. The most common adverse events of interest during years 1 and 2 of gilteritinib therapy were increased liver transaminase levels; adverse event incidence decreased in year 2. Thus, continued and post-HSCT gilteritinib maintenance treatment sustained remission with a stable safety profile. These findings confirm that prolonged gilteritinib therapy is safe and is associated with superior survival vs SC. This trial was registered at www. clinicaltrials. gov as #NCT02421939.
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Aniline Compounds ; Fms-like Tyrosine Kinase 3 ; Follow-Up Studies ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Pyrazines ; Recurrence
Publicat a:	Blood, Vol. 139 Núm. 23 (june 2022) , p. 3366-3375, ISSN 1528-0020

DOI: 10.1182/blood.2021011583
PMID: 35081255

10 p, 1.1 MB

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