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  3. 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

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

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Perl, A.E.
  • Larson, R.A.
  • Podoltsev, N.A.
  • Strickland, S.
  • Wang, E.S.
  • Atallah, E.
  • Schiller, G.J.
  • Martinelli, G.
  • Neubauer, A.
  • Sierra, J.
  • Recher, C.
  • Yoon, S.-S.
  • Maeda, Y.
  • Hosono, N.
  • Onozawa, M.
  • Kato, T.
  • Kim, H.-J.
  • Hasabou, N.
  • Nuthethi, R.
  • Tiu, R.
  • Levis, M.J.

Grupos

Abstract

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. © 2022 The American Society for Transplantation and Cellular Therapy

Datos de la publicación

ISSN/ISSNe:
2666-6375, 2666-6367

Transplantation and Cellular Therapy  ELSEVIER SCIENCE INC

Tipo:
Article
Páginas:
265-26510
PubMed:
36526260
Enlace a otro recurso:
www.scopus.com

Citas Recibidas en Web of Science: 35

Citas Recibidas en Scopus: 37

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Keywords

  • alanine aminotransferase; alkylating agent; anthracycline; aspartate aminotransferase; busulfan; CD135 antigen; creatine; creatine kinase; cyclophosphamide; cytarabine; gilteritinib; lactate dehydrogenase; midostaurin; purine derivative; sorafenib; aniline derivative; FLT3 protein, human; acute graft versus host disease; acute myeloid leukemia; adult; aged; anemia; arthralgia; Article; body weight gain; bone marrow suppression; cancer patient; cancer survival; cardiopulmonary insufficiency; controlled study; coughing; cumulative incidence; dermatomyositis; diarrhea; drug dose reduction; drug safety; drug tolerability; drug withdrawal; dry eye; dyspnea; engraftment; fatigue; female; fever; gene duplication; graft failure; graft recipient; graft survival; headache; heart arrest; heart ventricle tachycardia; hematopoietic stem cell transplantation; human; hyperglycemia; hypoalbuminemia; hypokalemia; leukemia relapse; leukemia remission; maintenance therapy; major clinical study; male; mor

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