CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review | Oncology | JAMA

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content="https://cdn.jamanetwork.com/ama/content_public/journal/jama/0/jrv240025f1_1730210269.65485.png?Expires=2147483647&Signature=nbh3~xeoCazeRtYgqDypHhhceNRbMdBTiTSMqMCufttj4vnOsTYX4vucex9sFKYa0WE6wM1BK7sEtbJYLI8YxWibQ4ny97J8YjomkX~TYijpUoyQWHF2erYece4owjz0WcMrYtK2xcRIxkP559HQ4wPJSQKRHoApOCDc4fWiXpmd8bH8xJJVsICDSdBA0DrBFjRdrzbuuFpv-2c8WAKFGcu8l-LsWmzUxFhEruO-Tnv5Y5Z1o-~U146o46ZH4jEccFjclM7~vrdQcQ4QWGRw3UTQ9w6Z28jIwyIh6-yh9JV0roefohWcVZIvvxA1VjQsUhGGt5IO7MaMUfKnXMpVQw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta name="citation_author" content="Jennifer N. Brudno" /><meta name="citation_author_institution" content="Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland" /><meta name="citation_author" content="Marcela V. Maus" /><meta name="citation_author_institution" content="Department of Medicine, Massachusetts General Hospital Cancer Center, Boston" /><meta name="citation_author" content="Christian S. Hinrichs" /><meta name="citation_author_institution" content="Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence, Rutgers Cancer Institute of New Jersey, New Brunswick" /><meta name="citation_title" content="CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review" /><meta name="citation_doi" content="10.1001/jama.2024.19462" /><meta name="citation_keyword" content="cancer" /><meta name="citation_keyword" content="hematologic neoplasms" /><meta name="citation_keyword" content="t-lymphocytes" /><meta name="citation_keyword" content="solid tumors" /><meta name="citation_keyword" content="t-cell therapy" /><meta name="citation_keyword" content="cell therapy" /><meta name="citation_keyword" content="chimeric antigen receptor t-cell therapy" /><meta name="citation_keyword" content="adverse effects" /><meta name="citation_keyword" content="burkitt's lymphoma" /><meta name="citation_keyword" content="neoplasms" /><meta name="citation_keyword" content="multiple myeloma" /><meta name="citation_keyword" content="lymphoma" /><meta name="citation_keyword" content="toxic effect" /><meta name="citation_keyword" content="cytokine release syndrome" /><meta name="citation_keyword" content="genetic engineering" /><meta name="citation_keyword" content="chemotherapy regimen" /><meta name="citation_keyword" content="b-lymphocytes" /><meta name="citation_keyword" content="leukemia, b-cell, acute" /><meta name="citation_keyword" content="chimeric antigen receptors" /><meta name="citation_keyword" content="follicular lymphoma" /><meta name="citation_keyword" content="mantle-cell lymphoma" /><meta name="citation_keyword" content="synovial sarcoma" /><meta name="citation_keyword" content="melanoma" /><meta name="citation_keyword" content="chronic b-cell leukemias" /><meta name="citation_keyword" content="surface antigens" /><meta name="citation_keyword" content="chronic lymphocytic leukemia" /><meta name="citation_abstract" content="<h3>Importance</h3><p>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.</p><h3>Observations</h3><p>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.</p><h3>Conclusions and Relevance</h3><p>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. 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</div> </div> </div>  </section> <section class="master-main"> <span class="hide tagmanagervalue" data-attribute="template" data-value="abstract" data-type="string"></span> <script type="application/ld+json"> { "@context": "https://schema.org/", "@type": "Article", "headline": "CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review", "author": "Jennifer N. 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href="/searchresults?author=Jennifer+N.+Brudno&q=Jennifer+N.+Brudno" rel=nofollow target="_blank">Jennifer N. Brudno, MD<sup>1</sup></a></span><span class='al-author-delim'>; </span><span class="wi-fullname brand-fg"><a href="/searchresults?author=Marcela+V.+Maus&q=Marcela+V.+Maus" rel=nofollow target="_blank">Marcela V. Maus, MD, PhD<sup>2</sup></a></span><span class='al-author-delim'>; </span><span class="wi-fullname brand-fg"><a href="/searchresults?author=Christian+S.+Hinrichs&q=Christian+S.+Hinrichs" rel=nofollow target="_blank">Christian S. Hinrichs, MD<sup>3</sup></a></span> </div> <div class="meta-author"> <a class="meta-author-title is-b stats-meta-author-toggle" data-tog-target=".meta-author-content">Author Affiliations</a> <a class="meta-articleinfo-jumplink section-jump-link scroll-to stats-scroll-to-articleinfo" data-tab-toggle=".tab-nav-full-text" href="#249980552">Article Information</a> <div class="meta-author-content"> <ul class="meta-author-affiliations"> <li class="meta-author-affiliation"> <div class="meta-author-name"><sup>1</sup>Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland</div> </li> <li class="meta-author-affiliation"> <div class="meta-author-name"><sup>2</sup>Department of Medicine, Massachusetts General Hospital Cancer Center, Boston</div> </li> <li class="meta-author-affiliation"> <div class="meta-author-name"><sup>3</sup>Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence, Rutgers Cancer Institute of New Jersey, New Brunswick</div> </li> </ul> </div> </div> <div class="meta-citation-wrap"> <span class="meta-citation-journal-name">JAMA. </span><span class="meta-citation"> Published online November 4, 2024. doi:10.1001/jama.2024.19462</span> </div> </div> <div class="widget-EditorsChoice widget-instance-AMA_EditorsChoice_Links"> </div> <div class="widget-LinkedContentToolbar widget-instance-AMA_LinkedContentToolbar"> <div class="linked-content-toolbar"> <div class="hidden js-search-open-multimedia-by-default" showContentByDefault="False"></div> <div class="linked-content-controls"> <a class="linked-content-trigger td-n stats-graphical-abstract" href="#graphical-abstract-tab"> <i class="icon-visual-abstract"><span class="sr-t">visual abstract icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Visual <div>Abstract</div></div> </a> <a class="linked-content-trigger td-n stats-editorial-comment" href="#editorial-comment-tab"> <i class="icon-document"><span class="sr-t">editorial comment icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Editorial <div>Comment</div></div> </a> <a class="linked-content-trigger td-n stats-related-articles" href="#related-articles-tab"> <i class="icon-related"><span class="sr-t">related articles icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Related <div>Articles</div></div> </a> <a class="linked-content-trigger td-n stats-author-interviews" href="#author-interviews-tab"> <i class="icon-author_interview"><span class="sr-t">author interview icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Interviews</div> </a> <a class="linked-content-trigger td-n stats-more-multimedia" href="#more-multimedia-tab"> <i class="icon-multimedia"><span class="sr-t">multimedia icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Multimedia</div> </a> <a class="linked-content-trigger td-n stats-listen-to-this-article" href="#listen-to-this-article-tab"> <i class="icon-audio"><span class="sr-t">audio icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Listen to <div>this article</div></div> </a> </div> <div class="linked-content-tabs"> <div id="graphical-abstract-tab" class="linked-content-tab graphical-abstract-tab"> <div class="widget-SectionDisplay widget-instance-AMA_GraphicalAbstract_Tab"> </div> </div> <div id="editorial-comment-tab" class="linked-content-tab editorial-comment-tab"> <div class="widget-ArticleLinks widget-instance-AMA_LinkedContentToolbar_EditorialComments"> <ul class="article-abstract-links related-abstract-content"> <li class="article-link related-abstract-article"> <a class="related-article-title" href="https://jamanetwork.com/journals/jama/fullarticle/2825804"> <div class="related-article-type">Editor's Note</div> <div class="related-article-title sb-tc">Translational Science Reviews—A New <i>JAMA</i> Review</div> </a> <div class="related-article-authors">Mary M. 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CAR T treatments improve overall survival for patients with large B-cell lymphoma and progression-free survival for patients with multiple myeloma.</span></p><p><strong>Observations</strong> <span>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.</span></p><p><strong>Conclusions and Relevance</strong> <span>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. 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