Outcomes in Patients with FLT3-Mutated Relapsed/ Refractory Acute Myelogenous Leukemia Who Underwent Transplantation in the Phase 3 ADMIRAL Trial of Gilteritinib versus Salvage Chemotherapy
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 (Medical College of Wisconsin)
Schiller, Gary J. (David Geffen School of Medicine at UCLA)
Martinelli, Giovanni (IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori "Dino Amadori" IRST S.r.l)
Neubauer, Andreas (Universitätsklinikum Giessen und Marburg GmbH)
Sierra, Jorge (Institut d'Investigació Biomèdica Sant Pau)
Montesinos, Pau (Hospital Universitari i Politècnic La Fe (València))
Recher, Christian (Centre Hospitalier Universitaire de Toulouse. Institut Universitaire du Cancer de Toulouse Oncopole. Université de Toulouse 3 Paul Sabatier)
Yoon, Sung-Soo (Seoul National University Hospital)
Maeda, Yoshinobu (Okayama University Hospital)
Hosono, Naoko (University of Fukui)
Onozawa, Masahiro (Hokkaido University)
Kato, Takayrasu (Department of Hematology. University of Tsukuba)
Kim, Hee-Je (Catholic Hematology Hospital. College of Medicine. The Catholic University of Korea)
Hasabou, Nahla (Astellas Pharma US. Inc.)
Nuthethi, Rishita (Astellas Pharma US. Inc.)
Tiu, Ramon (Astellas Pharma US. Inc.)
Levis, Mark J. (Sidney Kimmel Comprehensive Cancer Center. Johns Hopkins University)

Data:	2023
Resum:	The fms-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib improved the survival of patients with relapsed or refractory (R/R) FLT3-mutated acute myelogenous leukemia (AML) in the phase 3 ADMIRAL trial. In this study, we assessed survival and relapse rates of patients in the ADMIRAL trial who underwent hematopoietic stem cell transplantation (HSCT), as well as safety outcomes in patients who received post-transplantation gilteritinib maintenance therapy. ADMIRAL was a global phase 3 randomized controlled trial that enrolled adult patients with FLT3-mutated R/R AML. Patients with R/R AML who harbored FLT3 internal tandem duplication mutations in the juxtamembrane domain or D835/I836 point mutations in the tyrosine kinase domain were randomized (2:1) to gilteritinib (120 mg/day) or to preselected high- or low-intensity salvage chemotherapy (1 or 2 cycles). Patients in the gilteritinib arm who proceeded to HSCT could receive post-transplantation gilteritinib maintenance therapy if they were within 30 to 90 days post-transplantation and had achieved composite complete remission (CRc) with successful engraftment and no post-transplantation complications. Adverse events (AEs) during HSCT were recorded in the gilteritinib arm only. Survival outcomes and the cumulative incidence of relapse were assessed in patients who underwent HSCT during the trial. Treatment-emergent AEs were evaluated in patients who restarted gilteritinib as post-transplantation maintenance therapy. Patients in the gilteritinib arm underwent HSCT more frequently than those in the chemotherapy arm (26% [n = 64] versus 15% [n = 19]). For all transplantation recipients, 12- and 24-month overall survival (OS) rates were 68% and 47%, respectively. Despite a trend toward longer OS after pretransplantation CRc, post-transplantation survival was comparable in the 2 arms. Patients who resumed gilteritinib after HSCT had a low relapse rate after pretransplantation CRc (20%) or CR (0%). The most common AEs observed with post-transplantation gilteritinib therapy were increased alanine aminotransferase level (45%), pyrexia (43%), and diarrhea (40%); grade ≥3 AEs were related primarily to myelosuppression. The incidences of grade ≥III acute graft-versus-host disease and related mortality were low. Post-transplantation survival was similar across the 2 study arms in the ADMIRAL trial, but higher remission rates with gilteritinib facilitated receipt of HSCT. Gilteritinib as post-transplantation maintenance therapy had a stable safety and tolerability profile and was associated with low relapse rates. Taken together, these data support a preference for bridging therapy with gilteritinib over chemotherapy in transplantation-eligible patients.
Nota:	Financial disclosure: This study was funded by Astellas Pharma, Inc. Medical writing/editorial support was provided by Kalpana Vijayan, PhD, and Cheryl Casterline, MA, from Peloton Advantage, LLC, an OPEN Health company and funded by the study sponsor.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Acute myelogenous leukemia ; FLT3 mutation ; FLT3 inhibitor ; Hematopoietic stem cell ; Transplantation ; Post-transplantation mainte-nance therapy
Publicat a:	Transplantation and Cellular Therapy, Vol. 29 Núm. 4 (april 2023) , p. 265.e1-265.e10, ISSN 2666-6367

DOI: 10.1016/j.jtct.2022.12.006
PMID: 36526260

10 p, 903.6 KB

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