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4308 Role of Measurable Residual Disease (MRD) Testing for the Prediction of Late Relapses Following Allogeneic Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 617. Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster III
Hematology Disease Topics & Pathways:
Research, adult, AML, Acute Myeloid Malignancies, Clinical Research, Diseases, Myeloid Malignancies, Human, Study Population, Minimal Residual Disease
Monday, December 11, 2023, 6:00 PM-8:00 PM

Naveed Ali, MBBS1, Othus Megan, PhD2*, Eduardo Rodríguez-Arbolí, MD3*, Corentin Orvain3*, Filippo Milano, MD3, Brenda M. Sandmaier, MD3, Chris Davis1*, Ryan S. Basom1*, Frederick R. Appelbaum, MD1 and Roland B. Walter, MD, PhD, MS4,5,6

1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
2Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA
3Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA
4Translational Science and Therapeutics Division, Fred Hutchinson Cancer Research Center, Seattle, WA
5Division of Hematology, Department of Medicine, University of Washington, Seattle, WA
6Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA

BACKGROUND: Measurable residual disease (MRD) before and/or shortly after allogeneic hematopoietic cell transplantation (HCT) is an independent indicator of high post-HCT relapse risk in acute myeloid leukemia (AML). However, many relapses, particularly among patients with MRD, occur within the first 3 months after allografting, and the role of MRD testing in the identification of patients at risk of relapses occurring at later times is unknown.

METHODS: To address this uncertainty, we studied all adults ≥18 years with AML or MDS/AML based on 2022 International Consensus Classification criteria who received a first allograft while in first or second morphologic remission at a single institution between 4/2006 and 3/2023 and underwent MRD testing via multiparameter flow cytometry during the pre-HCT evaluation. In line with the performance characteristics of the assay, any detectable MRD was considered positive.

RESULTS: One thousand two hundred and sixty-two patients with AML (n=1,112 [88%]) or MDS/AML (n=150 [12%])underwent allograft following myeloablative (n=732 [58%]) or non-myeloablative (n=530 [42%]) conditioning regimens. Of these, 260 (21%) tested positive for MRD during the pre-HCT evaluation. With a median follow-up of 60.6 (range: 1.9-196.3) months after HCT among survivors, there were 589 deaths, 381 relapses, and 259 NRM events contributing to the probability estimates for relapse, overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) in this cohort. 239/1,262 patients (19%) experienced disease recurrence (n=181 [14%]) and/or death (n=89 [7%]) within the first 100 days after allografting. Relapse (P<0.001) and death (P=0.002) but not NRM (P=0.29) before day +100 were more common among patients with pre-HCT MRD. Of patients alive without relapse at day +100, 93% (954 of 1,023) underwent bone marrow restaging studies between day 70 and 100 post-HCT. Among these 954 patients, 146 (15%) had MRD before HCT, whereas only 25 (3%) had MRD at day +70-100 testing. The latter had a significantly higher 3-year relapse risk (37% vs. 18%; P=0.002), and worse RFS (17% vs. 68%; P<0.001) OS (16% vs. 72%; P<0.001) and NRM (46% vs. 14%; P<0.001) relative to the 929 patients without MRD; for results of univariate regression models, see Table 1. Importantly, however, while 130 of the 146 patients (89%) with MRD before HCT tested negative for MRD at day +70-100, their outcomes were substantially worse compared to patients who tested negative for MRD before HCT and at day +70-100, with 3-year relapse risk of 38% vs. 15% (P<0.001), 3-year RFS of 47% vs. 71% (P<0.001), and 3-year OS of 53% vs. 75% (P<0.001), whereas 3-year NRM estimates were similar (14% vs. 14% (P=0.21). Qualitatively similar results were obtained when the cohort was restricted to patients with AML, and also when comparing patients undergoing myeloablative conditioning with those undergoing non-myeloablative conditioning, with a statistically significantly higher relapse risk and lower RFS and OS but not NRM for patients with MRD before HCT but no MRD at day +70-100 compared to those who tested negative for MRD before HCT and at day +70-100 (Table 1).

CONCLUSION: For AML and MDS/AML patients alive without relapse at day +100 after allografting, MRD testing at day +70-100 post-HCT identifies patients at increased risk of relapse and worse survival, but only a small number of patients will test positive at this post-HCT timepoint. While a high proportion of patients with MRD before HCT will test negative for MRD at day +70-100, their outcomes are substantially inferior to patients without MRD both before and at day +70-100 after HCT. These data suggest that all patients with pre-HCT MRD should be considered for pre-emptive therapeutic strategies, ideally in the setting of well-controlled clinical trials, given their high risk of disease recurrence regardless of the post-HCT MRD information.

Disclosures: Milano: ExCellThera Inc.: Research Funding. Sandmaier: Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Walter: Amgen, Aptevo, Celgene, Janssen, Jazz, MacroGenics, Pfizer: Research Funding; ImmunoGen, Jura: Consultancy, Research Funding; Abbvie, Adicet, Amphivena, BerGenBio, Bristol Myers Squibb, GlaxoSmithKline, Orum: Consultancy.

*signifies non-member of ASH