Novel Composite Health Assessment Risk Model for Older Allogeneic Transplant Recipients: BMT-CTN 1704

• A novel CHARM was developed and validated in older patients to predict non-relapsemortality and survival after allogeneic transplants.

• CHARM performed better than HCT-CI per decision curve analysis for NRM.

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns about non-relapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study (BMT-CTN 1704) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the U.S. We analyzed associations between 13 measurements of older adult health and NRM within 1-year to construct a comprehensive health assessment risk model (primary-CHARM) using amultivariate Fine-Gray model and grouped penalized variable selection. Two (Cox and pseudovalue Boosting) Machine-Learning (ML) models were also explored. Models' performances were compared using area under the receiver operating curve (AUC), with bootstrap and crossvalidation sampling to correct for optimism, decision-curve analysis (DCA), calibration, and Brierscores. Among 1105 patients with median age of 67 years (range 60-82) who received alloHCT, NRM was 14.4% and overall survival (OS), 71.7% at 1-year. Factors statistically selected for inclusion in primary-CHARM were: higher comorbidity-burden, lower albumin, higher Creactive protein, older age, higher weight loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR]:2.72, p<0.0001) and worse OS (HR:2.09, p<0.0001). Bootstrap bias-corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM to HCTcomorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. The primary-CHARM, comprised of mostly simple and readily available parameters, risk-stratifies older adults for allo-HCT. Adopting primary-CHARM in practice maypromote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. Clinicaltrials.gov number: (NCT03992352).