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Review
Translational Science
November4, 2024
Jennifer N.Brudno,MD1; Marcela V.Maus,MD, PhD2; Christian S.Hinrichs,MD3
Author Affiliations Article Information
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1Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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2Department of Medicine, Massachusetts General Hospital Cancer Center, Boston
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3Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence, Rutgers Cancer Institute of New Jersey, New Brunswick
JAMA. Published online November 4, 2024. doi:10.1001/jama.2024.19462
- Editor's Note Translational Science Reviews—A New JAMA Review
Mary M.McDermott,MD; Kristin L.Walter,MD, MS; KirstenBibbins-Domingo,PhD, MD, MAS
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CAR T Cells and T-Cell Therapies for Cancer
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Abstract
Importance Chimeric antigen receptor (CAR) T cells are T lymphocytes that are genetically engineered to express a synthetic receptor that recognizes a tumor cell surface antigen and causes the T cell to kill the tumor cell. CAR T treatments improve overall survival for patients with large B-cell lymphoma and progression-free survival for patients with multiple myeloma.
Observations Six CAR T-cell products are approved by the US Food and Drug Administration (FDA) for 6 hematologic malignancies: B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma. Compared with standard chemotherapy followed by stem cell transplant, CAR T cells improved 4-year overall survival in patients with large B-cell lymphoma (54.6% vs 46.0%). Patients with pediatric acute lymphoblastic leukemia achieved durable remission after CAR T-cell therapy. At 3-year follow-up, 48% of patients were alive and relapse free. In people with multiple myeloma treated previously with 1 to 4 types of non–CAR T-cell therapy, CAR T-cell therapy prolonged treatment-free remissions compared with standard treatments (in 1 trial, CAR T-cell therapy was associated with progression-free survival of 13.3 months compared with 4.4 months with standard therapy). CAR T-cell therapy is associated with reversible acute toxicities, such as cytokine release syndrome in approximately 40% to 95% of patients, and neurologic disorders in approximately 15% to 65%. New CAR T-cell therapies in development aim to increase efficacy, decrease adverse effects, and treat other types of cancer. No CAR T-cell therapies are FDA approved for solid tumors, but recently, 2 other T lymphocyte–based treatments gained approvals: 1 for melanoma and 1 for synovial cell sarcoma. Additional cellular therapies have attained responses for certain solid tumors, including pediatric neuroblastoma, synovial cell sarcoma, melanoma, and human papillomavirus–associated cancers. A common adverse effect occurring with these T lymphocyte–based therapies is capillary leak syndrome, which is characterized by fluid retention, pulmonary edema, and kidney dysfunction.
Conclusions and Relevance CAR T-cell therapy is an FDA-approved therapy that has improved progression-free survival for multiple myeloma, improved overall survival for large B-cell lymphoma, and attained high rates of cancer remission for other hematologic malignancies such as acute lymphoblastic leukemia, follicular lymphoma, and mantle cell lymphoma. Recently approved T lymphocyte–based therapies demonstrated the potential for improved outcomes in solid tumor malignancies.
- Editor's Note Translational Science Reviews—A New JAMA Review
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Oncology Hematology Targeted and Immune Therapy Hematologic Cancer Clinical Pharmacy and Pharmacology Adverse Drug Events
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Brudno JN, Maus MV, Hinrichs CS. CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review. JAMA. Published online November 04, 2024. doi:10.1001/jama.2024.19462
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