Background: 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.
Objective: 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.
Study design: 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 2014‒2019. Patient, disease, and transplant characteristics were collected from CIBMTR (Center for International Blood & Marrow Transplant Research) between 2014‒2022. 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 CR (≥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, non-relapse 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.
Results: A total of 3147 eligible patients (CR1, n=2389; ≥CR2, n=340; R/R, n=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<0.001) associated with improved OS and LFS, and decreased probability of relapse; NRM likely differed across cohorts after alloHCT (p=0.003). 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 [1.19-1.72], p=0.0001, and 2.14 [1.88-2.44], p<0.0001, 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 [1.56-2.63], p<0.0001 and 3.98 [3.07-5.17], p<0.0001, 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 [1.82-3.33], p<0.0001 and 4.68 [3.46-6.34], p<0.0001, respectively). Disease status was not significantly associated with NRM. We also identified several additional patient, disease, and transplant characteristics that may be 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.
Conclusion: In this largest study to date of patients from the US 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.
Keywords: FLT3 inhibitor; acute myeloid leukemia; allogeneic hemopoietic cell transplantation; relapse; survival.
Copyright © 2024. Published by Elsevier Inc.