Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3 .

Autor:	Levis MJ; Johns Hopkins University, Baltimore, MD., Hamadani M; CIBMTR/Medical College of Wisconsin, Milwaukee, WI., Logan B; CIBMTR/Medical College of Wisconsin, Milwaukee, WI., Jones RJ; Johns Hopkins University, Baltimore, MD., Singh AK; University of Kansas, Kansas City, KS., Litzow M; Mayo Clinic, Rochester, MN., Wingard JR; University of Florida, Gainesville, FL., Papadopoulos EB; Memorial Sloan Kettering Cancer Center, New York, NY., Perl AE; University of Pennsylvania, Philadelphia, PA., Soiffer RJ; Dana-Farber Cancer Institute, Boston, MA., Ustun C; Rush University Medical Center, Chicago, IL., Ueda Oshima M; Fred Hutchinson Cancer Center, Seattle, WA., Uy GL; Washington University, St Louis, MO., Waller EK; Emory University, Atlanta, GA., Vasu S; Ohio State University, Columbus, OH., Solh M; Northside Hospital Cancer Institute, Atlanta, GA., Mishra A; Moffitt Cancer Center, Tampa, FL., Muffly L; Stanford University, Palo Alto, CA., Kim HJ; Catholic Hematology Hospital, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Mikesch JH; University of Muenster, Münster, Germany., Najima Y; Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan., Onozawa M; Hokkaido University Hospital, Sapporo, Japan., Thomson K; University College Hospital, London, United Kingdom., Nagler A; Chaim Sheba Medical Center, Tel Hashomer, Israel., Wei AH; Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Walter and Eliza Hill Institute of Medical Research and University of Melbourne, Melbourne, Australia., Marcucci G; Beckman Research Institute of City of Hope, Duarte, CA., Geller NL; National Heart, Lung and Blood Institute, Bethesda, MD., Hasabou N; Astellas Pharma Inc, Northbrook, IL., Delgado D; Astellas Pharma Inc, Northbrook, IL., Rosales M; Astellas Pharma Inc, Northbrook, IL., Hill J; Astellas Pharma Inc, Northbrook, IL., Gill SC; Astellas Pharma Inc, Northbrook, IL., Nuthethi R; Astellas Pharma Inc, Northbrook, IL., King D; The Emmes Company, Rockville, MD., Wittsack H; The Emmes Company, Rockville, MD., Mendizabal A; The Emmes Company, Rockville, MD., Devine SM; National Marrow Donor Program, Minneapolis, MN., Horowitz MM; CIBMTR/Medical College of Wisconsin, Milwaukee, WI., Chen YB; Massachusetts General Hospital, Boston, MA.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 May 20; Vol. 42 (15), pp. 1766-1775. Date of Electronic Publication: 2024 Mar 12.
DOI:	10.1200/JCO.23.02474
Abstrakt:	Purpose: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD ) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. Methods: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. Results: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). Conclusion: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.
Databáze:	MEDLINE
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