2024-05-02 バージニア工科大学(VirginiaTech)
◆「JAMA Oncology」に掲載されたこの研究は、急性骨髄性白血病(AML)の成人患者に対する化学療法が成功した後も体内に残るがん細胞の痕跡を示す「測定可能な残留疾患」の検査の重要性と実用性を強調しています。
◆バージニア工科大学の教授であるクリストファー・アワーガン氏は、「この検査は実現可能で、既存のキットを使って主要な病院のラボで実施可能だ」と述べています。
<関連情報>
- https://news.vt.edu/articles/2024/05/research-fbri-0502.html
- https://jamanetwork.com/journals/jamaoncology/article-abstract/2818452
急性骨髄性白血病に対する同種移植前の測定可能な残存FLT3内部タンデム重複について Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia
Laura W. Dillon, PhD; Gege Gui, ScM; Niveditha Ravindra, MD; et al
JAMA Oncology Published:May 2, 2024
DOI:10.1001/jamaoncol.2024.0985
Key Points
Question Are different levels of acute myeloid leukemia (AML) measurable residual disease (MRD) prior to allogeneic hematopoietic cell transplant (HCT) associated with different posttransplant clinical outcomes?
Findings In this cohort study including 537 patients, adults with AML in first remission prior to allogeneic HCT with persistence of FLT3 internal tandem duplication (ITD) at a variant allele fraction of 0.01% or higher had increased relapse and death compared with those with lower levels detected. Patients with no detectable FLT3-ITD had the best outcomes.
Meaning In this study, for adults with FLT3-ITD AML, there was a dose-dependent correlation between pretransplant level of persistent FLT3-ITD MRD and clinical outcomes.
Abstract
Importance Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown.
Objective To examine the association between pre–allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR.
Design, Setting, and Participants In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023.
Exposure Centralized DNA sequencing for FLT3-ITD in pre–allogeneic HCT first CR blood using a commercially available kit.
Main Outcomes and Measures The primary outcomes were overall survival and cumulative incidence of relapse, with non–relapse-associated mortality as a competing risk post–allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points.
Results Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning.
Conclusions and Relevance This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.
