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685 The Composite Health Risk Assessment Model (CHARM) Predicts Risks of Toxicities, Functional and Cognitive Decline Among Survivors of Allogeneic Hematopoietic Cell Transplantation (allo-HCT): A Prospective BMT-CTN Study 1704

Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Risk Adapted Approaches to Reduce Transplant Related Toxicities
Hematology Disease Topics & Pathways:
Research, AML, Acute Myeloid Malignancies, Adult, Elderly, Epidemiology, Clinical Research, Patient-reported outcomes, Diseases, Treatment Considerations, Adverse Events, Myeloid Malignancies, Human, Study Population
Sunday, December 8, 2024: 4:30 PM

Mohamed Sorror, MD, MSc1,2, Wael Saber, MD, MS3,4, Brent R. Logan, PhD5,6*, Nancy Geller, PhD7*, Anna Bellach, Ph.D.7*, Jianqun Kou, MS6,8*, William A. Wood, MD, MPH9, John M. McCarty, MD10, Thomas G. Knight, MD11, Lyndsey Runaas, MD12*, Laura Johnston, MD13, Jeremy Walston14*, Ryotaro Nakamura, MD15, Asmita Mishra, MD, MBA16, Joseph Uberti, MD, PhD17, Parastoo B Dahi, MD18,19*, Jennifer N. Saultz, DO20, Shannon R McCurdy, MD21, Lawrence E Morris, MD22, Philip Imus, MD23, William J. Hogan, MD24, Kalyan Nadiminti, MBBS25, Vijaya Raj Bhatt, MD26,27, Rebecca Olin, MD28, Joseph E. Maakaron, MD29, Ronald Sobecks, MD30, Sarah A. Wall, MD, MPH31, Deborah Mattila, BA32,33*, Bailey Protz32,33*, Steven Michael Devine, MD33,34, Mary M. Horowitz, MD6,32 and Andrew Artz, MD, MS35

1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
2Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA
3Center for International Blood and Marrow Transplant Research, Minneapolis, MN
4Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI
5Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, WI
6Medical College of Wisconsin, Milwaukee, WI
7National Heart, Lung, and Blood Institute, The Office of Biostatistics Research, Bethesda, MD
8CIBMTR® (Center for International Blood and Marrow Transplant Research), Milwaukee, WI
9Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
10Virginia Commonwealth University Massey Cancer Center, Richmond, VA
11Department of Hematologic Oncology and Blood Disorders, Atrium Health Levine Cancer Institute, Charlotte, NC
12Medical College of Wisconsin, Division of Hematology/Oncology, Milwaukee, WI
13Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA
14Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD
15Hematology and HCT, City of Hope National Medical Center, Duarte, CA
16Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
17Karmanos Cancer Institute, Detroit, MI
18Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY
19Department of Medicine, Weill Cornell Medical College, New York, NY
20Knight Cancer Institute, Oregon Health & Science University, Portland, OR
21Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
22Blood and Marrow Transplant Program, Northside Hospital Cancer Institute, Atlanta, GA
23Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD
24Division of Hematology, Mayo Clinic, Rochester, MN
25Carbone Cancer Center, University of Wisconsin Hospitals and Clinics, Madison, WI
26Division of Hematology-Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE
27The Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE
28University of California San Francisco, San Francisco, CA
29Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN
30Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
31Division of Hematology, The Ohio State University, Columbus, OH
32Center for International Blood and Marrow Transplant Research (CIBMTR), Minneapolis, MN
33National Marrow Donor Program, Minneapolis, MN
34Center for International Blood and Marrow Transplant Research, NMDP, Minneapolis, MN
35City of Hope National Medical Center, Duarte, CA

Introduction: The BMT CTN 1704 study developed and validated the CHARM that stratified risk for non-relapse mortality and overall mortality among older adults, performing better than the HCT-CI alone (Artz A et al, Blood. 2023;142:109) and equally to two machine learning models. CHARM assigns a total score for 7 health variables: increasing age, higher HCT-CI scores, lower albumin, higher C-reactive protein, higher percent of weight loss over the preceding year, lower patient-reported performance status scores, and lower cognitive score per Montreal cognitive assessment (MoCA). A CHARM calculator is available at:https://cibmtr.org/CIBMTR/OffNav/DevSandbox/CHARM-Risk-NRM-Calculator

No multi-institutional prospective data exist on functional trajectories and morbidity after HCT in older patients. We now report on the association of CHARM to trajectories of secondary morbidity outcomes among allo-HCT survivors of this large, prospective study.

Patients and Methods: Allo-HCT candidates, aged ≥60 years (yrs), were enrolled (n=1226) from 49 centers in the US between 2019 - 2021. The primary analysis includes 1105 patients proceeding to allo-HCT on study and secondary endpoints were assessed at day (D) 100, 180 and 365 except MoCA and organ toxicity were restricted to D100 and frailty had inadequate data for D100. A sequential multiple imputation strategy was implemented to impute endpoints for survivors at each time point with missing data. Analyses on multiply imputed datasets were conducted and the results combined using Rubin’s rule. Associations between CHARM scores and secondary outcomes were analyzed using a multivariable Cox, Fine-Gray, Generalized Estimating Equations, and logistic regression model for survival, competing risks, continuous, and binary outcomes, respectively, with latter two focused on surviving patients. Models were adjusted for other variables including conditioning intensity, graft-versus-host disease (GVHD) prophylaxis regimen, disease-risk index, donor-recipient gender match, ethnicity, baseline value of the dependent variable, and visit timepoints.

Results:

Higher CHARM scores were associated with development of serious organ toxicities by D100 (OR: 2.05, [1.52-2.78], p<0.0001) and ≥2 worsening score on the MoCA (odds ratio (OR) 1.55 [1.16-2.1], p=0.003).

Among survivors at all timepoints, higher CHARM scores were associated with greater disability by instrumental activities of daily living (IADL) (Slope -0.640 [-0.433-0.846], p<0.001) and worsening Patient-Reported Outcomes Measurement Reporting System (PROMIS) physical function (Slope -0.981 [-0.057 - -1.904], p=0.037), depression (Slope 0.763 [0.042-1.484], p=0.038) and in a lesser magnitude anxiety (Slope 0.659, p=0.076).

Among survivors at D180 and D365, higher CHARM scores were associated with worse frailty (Slope 0.193 [0.081-0.305], p<0.001).

CHARM scores were not associated with development of acute GVHD grades 2-4 or 3-4 but were associated with post-GVHD increased mortality (HR: 1.61, [1.25-2.08], p=0.0002). Higher CHARM scores are associated with a lower incidence of chronic GVHD (HR: 0.83, p=0.026), likely due to the effect of CHARM on the competing risk of death leaving fewer patients at risk for chronic GVHD.

Conclusions: The novel primary CHARM, originally developed to predict risks of NRM, also predicts worse frailty, disability, cognitive decline, and serious organ toxicities; outcomes that are critically important to older recipients of allo-HCT. CHARM therefore informs risks of transplant morbidity, separate from risks of developing acute GVHD. Results further support adopting CHARM in practice to counsel patients, expedite HCT referrals for lower risk CHARM, and design trials for high CHARM score patients.

Disclosures: Sorror: JAZZ pharmaceuticals: Consultancy, Honoraria. Logan: Sanofi: Consultancy; Geron Corporation: Consultancy; Jansen: Consultancy. Wood: Pfizer: Research Funding; Genetech: Research Funding; ASH Research Collaborative: Consultancy; Koneksa Health: Consultancy, Current equity holder in publicly-traded company; Teledoc Health: Consultancy. Nakamura: Pfizer: Consultancy; Helocyte: Research Funding; Ono Pharmaceutical: Consultancy; Mitarisan: Research Funding; Omeros (ended): Consultancy; Blue Bird (ended): Consultancy; Sanofi: Consultancy; Maat Pharma: Research Funding. Mishra: Novartis: Research Funding. Saultz: Sanofi: Consultancy; Ikena: Research Funding; Rigel: Consultancy. Imus: Janssen: Research Funding. Olin: Rigel: Consultancy; Cellectis: Research Funding; Servier: Consultancy. Maakaron: Scripps Research Institute: Research Funding; Precision Biosciences: Research Funding; CRISPR: Research Funding; Atara: Research Funding; Gilead: Research Funding; VOR Bio: Research Funding; Affimed: Research Funding. Sobecks: CareDx, Inc: Membership on an entity's Board of Directors or advisory committees. Wall: Sobi: Speakers Bureau. Devine: National Marrow Donor Program: Current Employment. Horowitz: Janssen: Research Funding; Medac: Research Funding; CSL Behring: Research Funding; Gamida Cell: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Sanofi: Research Funding; Sobi: Research Funding; Xenikos: Research Funding; Astellas: Research Funding; Bristol-Myers Squibb: Research Funding. Artz: Magenta Therapeutics: Honoraria; Abbvie: Consultancy; Astra Zeneca: Honoraria.

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