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109 The Composite Health Risk Assessment Model (CHARM) to Predict 1-Year Non-Relapse Mortality (NRM) Among Older Recipients of Allogeneic Transplantation: A Prospective BMT-CTN Study 1704

Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Improving Outcomes by Reducing Transplant-Related Complications
Hematology Disease Topics & Pathways:
adult, elderly, Study Population, Human
Saturday, December 9, 2023: 9:30 AM

Andrew Artz, MD, MS1, Brent R. Logan, PhD2*, Wael Saber, MD, MS3, Nancy Geller, PhD4*, Anna Bellach, Ph.D.4*, Jianqun Kou, MS5*, William Wood, MD, MPH6, John M. McCarty, MD7, Thomas G. Knight, MD8, Lyndsey Runaas9*, Laura Johnston10, Jeremy Walston11*, Ryotaro Nakamura, MD12, Tammy Schuler13*, Asmita Mishra, MD, MBA14, Joseph Uberti, MD, PhD15, Parastoo B. Dahi, MD16*, Jennifer N. Saultz, DO17, Shannon R McCurdy, MD18, Lawrence Morris, MD19, Philip Imus, MD20, William J. Hogan, MD21, Kalyan Nadiminti, MBBS22, Vijaya Raj Bhatt, MD23, Deborah Mattila, BA24*, Bailey Protz25*, Steven M. Devine, MD26, Mary M. Horowitz, MD27 and Mohamed Sorror, MD, MSc28

1City of Hope, Duarte, CA
2Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI
3Medical College of Wisconsin, Milwaukee, WI
4National Heart, Lung, and Blood Institute, Bethesda, MD
5CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
6Division of Hematology, Department of Medicine, University of North Carolina At Chapel Hill Hospital, Chapel Hill, NC
7Virginia Commonwealth University Medical Center, Richmond, VA
8Department of Hematologic Oncology and Blood Disorders, Atrium Health Levine Cancer Institute, Charlotte, NC
9Froedtert Hospital, Milwaukee, WI
10Stanford University, Stanford, CA
11Johns Hopkins University, Baltimore, MD
12Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Comprehensive Cancer Center, Duarte, CA
13Fred Hutchinson Cancer Research Center, Seattle, WA
14Moffitt Cancer Center, Tampa, FL
15Karmanos Cancer Institute/Wayne State University, Detroit, MI
16Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
17Oregon Health & Science University, Portland, OR
18Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
19Blood and Marrow Transplant Program, Northside Hospital Cancer Institute, Atlanta, GA
20Johns Hopkins, Baltimore, MD
21Division of Hematology, Mayo Clinic, Rochester, MN
22Department of Medicine Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin–Madison, Madison, WI
23The Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE
24National Marrow Donor Program/Be The Match, Center for International Blood and Marrow Transplant Research, Minneapolis, MN
25National Marrow Donor Program/Be The Match, Center for International Blood and Marrow Transplant Research, Minnneapolis, MN
26Be the Match Foundation, Minneapolis, MN
27Center for International Blood and Marrow Transplant Research, Milwaukee, WI
28Fred Hutchinson Cancer Center, Seattle, WA

Introduction: Allogeneic hematopoietic cell transplantation (HCT) remains the only therapy for long-term disease control for many high-risk hematologic malignancies (HM). HCT use in older HM patients (pts) continues to increase. However, concerns of excessive transplant-related morbidity and non-relapse mortality (NRM) limit referrals and broader application of curative intent HCT. The HCT-comorbidity index (HCT-CI) was initially developed to improve risk-stratification of NRM. More recently, geriatric assessment (GA) and biomarkers have emerged as promising additional tools that may refine estimates of these risks. We hypothesized that a combination of health assessments by GA and biomarkers would constitute a robust and valid model, CHARM, for accurate personalized estimation of one-year (1-yr) NRM. Here, we report the results of the largest, first of its kind, prospective study of older recipients of HCT through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1704 study (NCT03992352).

Patients and Methods: Adults aged ≥60 years (yrs) with HM institutionally eligible for HCT were enrolled (n=1226) from 49 centers in the US between 2019 - 2021. Within 21 days of conditioning, 13 prospectively identified older pt.-specific health variables, informed from prior studies, were collected: age, HCT-CI, % of weight loss over the past yr, pt reported Karnofsky performance status, PROMIS physical function scale, instrumental activities of daily living (IADL), number of falls, PROMIS depression scale, number of prescribed medications, 4-meter walk speed, cognition by the Montreal Cognitive Assessment (MoCA), C-reactive protein (CRP) and albumin. The CHARM score to predict NRM within 1 yr was built using a multivariable (MVA) Fine-Gray model, with multiple imputation to handle modest missingness in covariates and grouped penalized variable selection using SCAD to identify variables to retain in the model. Final variables were used as continuous. The model further considered adjustment for conditioning intensity, CMV serostatus, and donor type. Area under the ROC curve (AUC) was calculated to validate the CHARM and compare to HCT-CI alone, with bootstrap sampling to correct for optimism in the within-sample AUC. MVA of overall survival (OS) within 1 yr used the CHARM score and adjusted for other significant variables derived from stepwise regression.

Results: The primary analysis included 1105 pts who were confirmed eligible and proceeded to transplant. Median age was 67 (range 60-82) and 32% were ≥ 70 yrs. AML (45%) and MDS (30%) were the most common indications and matched donors the most frequent donor type at 72%. Reduced intensity conditioning with fludarabine (flu)-melphalan (38%) and flu-busulfan (20%) were the most common regimens. Baseline geriatric vulnerabilities among evaluable pts were frequent including slow walk speed (<0.8 meter/second) in 22%, any IADL limitation in 37%, and cognitive impairment (MoCA < 23) in 12%. 1-yr NRM was lower than expected at 14.4% with 1-yr OS of 72%.

In the MVA model, albumin, CRP, HCT-CI, and weight loss were independently associated with NRM (Table) and comprised the CHARM. Of note, increasing age did not significantly affect NRM. The CHARM had within sample and bootstrap corrected AUC of 0.641 and 0.607 whereas the HCT-CI alone achieved corresponding AUC values of 0.601 and 0.598. NRM by tertiles is shown in Figure. Each point increase in the CHARM (median -2.2504, range -3.6327 to 0.1381), was associated with a hazard ratio (HR) of 2.83 (95% CI 2.12 – 3.78, p < 0.0001) for NRM. The CHARM also predicted overall mortality within 1-yr with a HR of 2.04 (1.65– 2.53, p <0.0001) per one point increase, independent of the disease risk index, which had a HR of 1.5 (95% CI 1.12 – 1.99, p =0.0059) for high/very high vs low/intermediate categories.

Conclusions: We report on the first prospectively established tool, CHARM, to risk-stratify older adult HCT comprised of simple and readily available parameters in transplant and oncology clinics. Adopting CHARM in practice may promote HCT referrals and access for older pts, given low risks of NRM among CHARM lower 2/3rd tertiles. Identifying high-risk CHARM pts pre-HCT will promote developing novel strategies to reduce NRM. Further analysis of the impacts of the 13 health assessment variables on geriatric morbidity such as disability trajectories is in-process.

Disclosures: Artz: Astra Zeneca: Other: Advisory Board; Magenta Therapeutics: Other: Advisory Board; Radiology Partner: Current equity holder in private company, Other: Spouse equity interest; Abbvie: Consultancy. Logan: Enlivex: Consultancy. Wood: Genetech: Research Funding; Pfizer: Research Funding; Teladoc: Consultancy; Koneksa Health: Consultancy; Quantum Health: Consultancy. Nakamura: Sanofi: Consultancy; Napajen: Consultancy; Blue Bird: Consultancy; Miyarisan: Research Funding; NCCN: Other: guideline panel for HCT; Jazz Pharmaceuticals: Consultancy, Other: research collaboration; Leukemia & Lymphoma Society: Other: grant reviewer; NCTN Lymphoma Steering Committee: Membership on an entity's Board of Directors or advisory committees; BMT CTN Steering Committee: Membership on an entity's Board of Directors or advisory committees; Omeros: Consultancy; Mt. Sinai: Other: Acute GVHD; International Consortium: Other: consortium chair. Saultz: Rigel: Other: Advisory Board; IKENA Oncology: Research Funding. Nadiminti: Abbvie: Research Funding. Bhatt: Novartis, Pfizer, Chimerix: Other; Abbvie, Incyte, Genentech, SERVIER, Protagonist Therapeutics and Imugene.: Consultancy; Incyte, Tolero Pharmaceuticals, National Marrow Donor Program, Abbvie, Pfizer, Jazz Pharmaceuticals.: Research Funding. Sorror: JAZZ pharmaceuticals: Consultancy; BlueNote and Massachusetts General Hospital: Research Funding.

OffLabel Disclosure: Most medications used for allogeneic transplantation are not approved. Fludarabine, melphalan, busulfan, tacrolimus, cyclophosphamide, total body irradiation are the drugs anticipated to be discussed.

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