New comorbidity index associated with survival after chimeric antigen receptor T-cell therapy for large B-cell lymphoma

The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T-cell (CAR-T) therapy is not well established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017 to 2020 were selected from the Center for International Blood and Marrow Transplant Research registry. Patients were randomly assigned to training or validation cohorts. Comorbidities given weighted scores comprised the CT-CI, which was then validated for overall survival (OS) prognostication. A total of 1916 patients from 97 medical centers were included, with a median age of 64 years (19-91 years). About 70% of patients had comorbidities, such as cardiac disease (12%); diabetes (14%); hepatic dysfunction (mild, 8%; moderate to severe, 2%); psychiatric disturbance (18%); and pulmonary dysfunction (moderate, 15%; severe, 12%). The CT-CI was calculated, stratified patients in 3 categories, and was associated with increased mortality. Patients with higher CT-CI scores had worse OS (CT-CI 1: hazard ratio [HR], 1.37 [95% confidence interval [CI], 1.16-1.62; P < .001]; CT-CI 2: HR, 1.49 [95% CI, 1.17-1.89; P = .001]; CT-CI ≥ 3: HR, 2.55 [95% CI, 1.90-3.42; P< .001]). Higher CT-CI scores predicted treatment-related mortality and relapse. There was no correlation between the CT-CI score and CAR-T-related toxicities. The novel CT-CI score stratifies the effect of patient comorbidities on survival after CAR-T therapy and can be used for clinical decision-making and treatment selection in high-risk populations. However, comorbidities and fear of increased toxicity should not preclude patients from this effective therapy.

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Publication Details

Journal
Blood Advances
Published
2025-08-14
DOI
https://doi.org/10.1182/bloodadvances.2024015599
Citations
2
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
2.09

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article

New comorbidity index associated with survival after chimeric antigen receptor T-cell therapy for large B-cell lymphoma

Martina Pennisi, Christopher Sun Strouse, Mahmoud Elsawy, Michael David Jain et al.
2 citations
Blood Advances
CAR-T cell therapy research
2.09
article

New comorbidity index associated with survival after chimeric antigen receptor T-cell therapy for large B-cell lymphoma

Martina Pennisi, Christopher Sun Strouse, Mahmoud Elsawy, Michael David Jain, Peter A. Riedell, Hamza Hashmi, Mohamed L. Sorror, Praveen Ramakrishnan Geethakumari, Frederick Lundry Locke, Amanda F. Cashen, Roni Shouval, Amer Beitinjaneh, Sairah Ahmed, Peiman Hematti, Tania Jain, Joseph P. McGuirk, Siddhartha Ganguly, LaQuisa C. Hill, Alberto Mussetti, Elizabeth J. Shpall, Bhagirathbhai Dholaria, Premal Lulla, Kitsada Wudhikarn, Wael Saber, Pere Barba, Farrukh T. Awan, Taiga Nishihori, Uri Greenbaum, Merav Bar, Amanda Olson, Veronika Bachanová, Adam S. Kittai, Partow Kebriaei, Margarida Magalhaes‐Silverman, Talha Badar, Temitope Oloyede, Miguel‐Angel Perales, Marcelo C. Pasquini, Jessica Foglesong, Amy Moskop, Cameron J. Turtle, Soyoung Kim, Umar Farooq, Elena Mead, Anusha Valluripalli
article en
2 citations

Abstract

The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T-cell (CAR-T) therapy is not well established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017 to 2020 were selected from the Center for International Blood and Marrow Transplant Research registry. Patients were randomly assigned to training or validation cohorts. Comorbidities given weighted scores comprised the CT-CI, which was then validated for overall survival (OS) prognostication. A total of 1916 patients from 97 medical centers were included, with a median age of 64 years (19-91 years). About 70% of patients had comorbidities, such as cardiac disease (12%); diabetes (14%); hepatic dysfunction (mild, 8%; moderate to severe, 2%); psychiatric disturbance (18%); and pulmonary dysfunction (moderate, 15%; severe, 12%). The CT-CI was calculated, stratified patients in 3 categories, and was associated with increased mortality. Patients with higher CT-CI scores had worse OS (CT-CI 1: hazard ratio [HR], 1.37 [95% confidence interval [CI], 1.16-1.62; P < .001]; CT-CI 2: HR, 1.49 [95% CI, 1.17-1.89; P = .001]; CT-CI ≥ 3: HR, 2.55 [95% CI, 1.90-3.42; P< .001]). Higher CT-CI scores predicted treatment-related mortality and relapse. There was no correlation between the CT-CI score and CAR-T-related toxicities. The novel CT-CI score stratifies the effect of patient comorbidities on survival after CAR-T therapy and can be used for clinical decision-making and treatment selection in high-risk populations. However, comorbidities and fear of increased toxicity should not preclude patients from this effective therapy.

Blood AdvancesVol. 10(1)
Hebron University (PS), Universitat Autònoma de Barcelona (ES), Ben-Gurion University of the Negev (IL), University of Iowa (US), The University of Sydney (AU), Dalhousie University (CA), University of Minnesota (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Miltenyi Biotec (Germany) (DE), Johns Hopkins University (US), Emory University (US), Chulalongkorn University (TH), Baylor College of Medicine (US), University of Washington (US), Medical College of Wisconsin (US), Washington University in St. Louis (US), Cornell University (US), University of South Florida (US), University of Minnesota System (US), Soroka Medical Center (IL), Jacksonville College (US), University of Iowa Hospitals and Clinics (US), WinnMed (US), Moffitt Cancer Center (US), University of Chicago (US), Institut d'Investigació Biomédica de Bellvitge (ES), Fred Hutch Cancer Center (US), Methodist Hospital (US), Southwestern Medical Center (US), The University of Kansas Cancer Center (US), Piedmont Cancer Institute (US), University of Miami Health System (US), Institut Català d'Oncologia (ES), Methodist Hospital (US), Versiti Blood Center of Wisconsin (US), Lurie Children's Hospital (US), Tisch Hospital (US), Vall d'Hebron Hospital Universitari (ES), Mayo Clinic in Florida (US), Texas Children's Hospital (US), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Sylvester Comprehensive Cancer Center (US), Sidney Kimmel Comprehensive Cancer Center (US), The University of Texas Southwestern Medical Center (US), Vanderbilt University Medical Center (US), Icahn School of Medicine at Mount Sinai (US)
Amgen, Bristol-Myers Squibb, Pfizer, Massachusetts General Hospital, Gilead Sciences, Fred Hutchinson Cancer Research Center, Celgene, Memorial Sloan-Kettering Cancer Center, Karyopharm Therapeutics, Moffitt Cancer Center, Cidara Therapeutics, Jazz Pharmaceuticals, Society for Immunotherapy of Cancer, bluebird bio, BeiGene, Incyte, Omeros Corporation, Astellas Pharma, Servier, Swedish Orphan Biovitrum, National Institutes of Health, Genentech, Pharmacyclics, Juno Therapeutics, Legend Biotech, National Cancer Institute, Eurostars
Good health and well-being
Openalex Percentile: Top 11%
CAR-T cell therapy research
2.09
DOIOpen Access PDFOpenAlex
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