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4315 Relative Prognostic Value of Flow Cytometric Measurable Residual Disease before Allogeneic Hematopoietic Cell Transplantation for Adults with MDS/AML or AML

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:
Minimal Residual Disease
Monday, December 11, 2023, 6:00 PM-8:00 PM

Corentin Orvain1*, Naveed Ali, MBBS2, Megan Othus, PhD3, Eduardo Rodríguez-Arbolí, MD4*, Filippo Milano, MD5, Brenda M. Sandmaier, MD6, Bart L. Scott, MD7, Frederick R. Appelbaum, MD7 and Roland B. Walter, MD, PhD, MS8

1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Angers, France
2Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
3Public Health Science Division, Fred Hutchinson Cancer Center, Seattle, WA
4Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, University of Seville, Seville, Spain
5Fred Hutchinson Cancer Research Center, Seattle, WA
6Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA
7Fred Hutchinson Cancer Center, Seattle, WA
8Translational Science and Therapeutics Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Background: Measurable residual disease (MRD), assessed by multiparameter flow cytometry (MFC) before allogeneic hematopoietic cell transplantation (HCT), is strongly and independently associated with poor post-HCT outcomes in adults with acute myeloid leukemia (AML). On the other hand, the relative prognostic value of MFC-based MRD testing is unknown in patients with myelodysplastic neoplasm (MDS)/AML, a disease entity newly defined by the 2022 International Consensus Classification (ICC) that encompasses cases of MDS with 10-19% blasts and recognizes the diagnostic continuum between MDS and AML.

Methods: To assess the relationship between pre-HCT, disease type, and post-HCT outcomes, we retrospectively analyzed 1,262 adults ≥18 years with MDS/AML (n=150) or AML (n=1,112), based on the ICC 2022 criteria, who received a first allograft while in first or second morphologic remission at a single institution between 4/2006 and 3/2023.

Results: The MDS/AML and AML cohorts differed significantly regarding patient and disease-specific characteristics, including age at HCT (60 vs. 56 years in MDS/AML and AML patients, respectively, P<0.001), HCT-CI score (P<0.001), adverse cytogenetic risk according to ELN 2022 criteria (39% vs. 26%, P<0.001), intensive therapy prior to allogeneic HCT (69% vs. 97%, P<0.001), time from last remission (76 vs. 98 days, P<0.001), first remission status (97% vs. 77%, P<0.001), pre-HCT MRD by MFC (35% vs. 19%, P<0.001), and peripheral blood stem cells as graft source (89% vs. 80%, P=0.015). There were no differences in donor source or conditioning intensity. With a median follow-up of 5.11 years (interquartile range [IQR]: 2.38-9.66) in survivors, there were 384 relapses, 590 deaths, and 258 non-relapse mortality (NRM) events contributing to the estimates for relapse, NRM, relapse-free survival (RFS), and overall survival (OS). At three years, NRM (21% [14-28%] for MDS/AML vs. 16% [14-19%] for AML, P=0.19), relapse (29% [22-36%] vs. 29% [27-32%], P=0.94), RFS (50% [42-59%] vs. 54% [51-58%], P=0.25), and OS (52% [44-61%] vs. 60% [57-63%], P=0.09) were similar between the two groups. After multivariable adjustment, relapse rates for patients with MDS/AML vs. those with AML were similar (hazard ratio [HR]=0.77 [0.50-1.17], P=0.2), as were NRM (HR=1.41 [0.91-2.18), P=0.12), RFS (HR=0.99 [0.73-1.35], P>0.9) and OS (HR=1.17 [0.85-1.61], P=0.3). Importantly, a significant interaction was found between pre-HCT MRD status and disease type (MDS/AML vs. AML) for relapse (P=0.009), RFS (P=0.013), and OS (P=0.048). The interaction models indicated that the HRs for the association between pre-HCT MRD and post-HCT outcomes were lower in patients with MDS/AML (for relapse: HR=1.73 [0.96-3.11] in MDS/AML vs. HR=3.56 [2.90-4.38], in AML; for RFS: HR=1.60 [1.03-2.48] vs. HR=2.67 [2.25-3.16]; for OS: HR=1.53 [0.97-2.39] vs. HR=2.34 [1.96-2.78]). Pre-HCT MRD was associated with a higher risk of relapse in both MDS/AML and AML patients but to a lesser extent in the MDS/AML patients. In these patients, relapse at three years was 37% [24-51%] for those with pre-HCT MRD vs. 24% [16-33%] for those without (P=0.068), translating into lower RFS (39% [28-56%] vs. 56% [47-67%], P=0.038) and OS (41% [29-58%] vs. 58% [48-70%], P=0.066) in MDS/AML patients with pre-HCT MRD. For comparison, in patients with AML, relapse at three years was 22% [20-25%] for those without MRD vs. 56% [50-62%] for those with (P<0.001), translating into lower RFS (27% [22-31%] vs. 61% [58-64%], P<0.001) and OS (35% [29-42%] vs. 65% [62-68%], P<0.001) in those with pre-HCT MRD. In line with these findings, C-statistics showed that pre-HCT MRD was not as predictive in MDS/AML patients in comparison to AML patients (for relapse: 0.57 in MDS/AML patients vs. 0.62 in AML patients; for RFS: 0.57 vs. 0.59; for OS: 0.56 vs. 0.58).

Conclusion: Our data suggest that, overall, patients with MDS/AML or AML in first or second morphologic remission have similar outcomes following allogeneic HCT. However, MFC-based pre-HCT MRD testing is prognostically substantially less informative for MDS/AML than AML patients, possibly because of increased rates of misclassification. These findings support the rationale to examine the prognostic value of molecular MRD testing in patients with MDS/AML.

Figure. Cumulative incidence of relapse stratified (A) by disease type at diagnosis and (B) by disease type at diagnosis and pre-HCT MRD.

Disclosures: Milano: ExCellThera Inc.: Research Funding. Sandmaier: Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Scott: BMI: Consultancy; Alexion: Consultancy; incyte: Speakers Bureau; Apellis: Consultancy, Honoraria. 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