Clinical Outcomes and Treatment Patterns in Adults With FLT3-ITDmut+ Acute Myeloid Leukemia Undergoing Allogeneic Hemopoietic Cell Transplantation in the United States and Canada.
Transplant Cell Ther
; 30(7): 683.e1-683.e13, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38663769
ABSTRACT
Allogeneic hematopoietic cell transplantation (alloHCT) is used to treat patients with acute myeloid leukemia (AML) with internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITDmut+). However, the effect of different characteristics on outcomes after transplant is not fully understood. The aim of this study was to determine the impact of patient, disease, and transplant characteristics on clinical outcomes and trends in maintenance therapy for patients with FLT3-ITDmut+ AML who underwent their first alloHCT. This was an observational cohort study of adults ≥18 years who were recipients of human leukocyte antigen identical sibling, haploidentical, 8/8 or 7/8 unrelated, or cord blood donor alloHCT in the United States and Canada between 2014 and 2019. Patient, disease, and transplant characteristics were collected from Center for International Blood & Marrow Transplant Research between 2014 and 2022. Patients enrolled in the MORPHO clinical trial (NCT02997202) were excluded. Clinical outcomes were measured from the time of alloHCT by disease status first complete remission (CR1), second or greater complete remission (≥CR2), or relapsed/refractory (R/R). The primary endpoints of this study were overall survival (OS) and leukemia-free survival (LFS). Key secondary endpoints included relapse after alloHCT, nonrelapse mortality (NRM), time from diagnosis to complete remission, time from complete remission to alloHCT, and maintenance therapy before and after alloHCT. Univariate analyses were conducted with Gray's test and log-rank test, while multivariable analyses were conducted using Cox proportional hazards models. A total of 3147 eligible patients (CR1, nâ¯=â¯2389; ≥CR2, nâ¯=â¯340; R/R, nâ¯=â¯418) were included. Most patient, disease, and transplant characteristics were similar between different disease statuses. In univariate analyses, disease status of CR1 compared with ≥CR2 or R/R was significantly (P < .001) associated with improved OS and LFS, and decreased probability of relapse; NRM likely differed across cohorts after alloHCT (Pâ¯=â¯.003). In multivariable analyses, patients with a disease status of ≥CR2 and R/R compared with CR1 had significantly shorter OS (hazard ratio [HR] 95% confidence interval [CI], 1.43 [1.19 to 1.72], Pâ¯=â¯.0001, and 2.14 [1.88 to 2.44], P < .0001, respectively). Patients with a disease status of CR1 at ≤2.6 months had better LFS compared with ≥CR2 and R/R (HR [95% CI], 2.03 [1.56 to 2.63], P < .0001 and 3.98 [3.07 to 5.17], P < .0001, respectively). Patients with a ≥CR2 or R/R disease status at ≤2.6 months had an increased likelihood of relapse compared with CR1 (HR [95% CI], 2.46 [1.82 to 3.33], P < .0001 and 4.68 [3.46 to 6.34], P < .0001, respectively). Disease status was not significantly associated with NRM. We also identified several additional patient, disease, and transplant characteristics that may have been associated with inferior OS and/or LFS and greater relapse and/or NRM. Maintenance therapy usage after alloHCT increased from 2014 to 2019 primarily due to increased FLT3 inhibitor use. In this largest study to date of patients from the United States and Canada with FLT3-ITDmut+ AML, disease status of CR1 at the time of alloHCT was associated with better clinical outcomes. Additional factors were identified that may also impact clinical outcomes, and in total, have the potential to inform clinical decision-making.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante Homólogo
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Leucemia Mieloide Aguda
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Transplante de Células-Tronco Hematopoéticas
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Tirosina Quinase 3 Semelhante a fms
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Transplant Cell Ther
Ano de publicação:
2024
Tipo de documento:
Article