chimeric antigen-receptor (CAR) T-cell therapy
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Indications
- hematopoietic malignancies
- refractory acute lymphoblastic leukemia* FDA-approved 8/2017)[7][13]
- refractory large B-cell lymphoma (FDA-approved Oct 2017)[12][13]
- multiple myeloma targeting BCMA[10]
- relapsed or refractory T-cell acute lymphoblastic leukemia[17]
- investigational treatment of refractory systemic lupus erythematosus[18]
- investigational treatment of aging through removal of senescent cells targeting cell-surface uPAR[20]
* B-cell precursor acute lymphoblastic leukemia
Contraindications
- only 26% of patients with relapsed/refractory CLL respond[11]
* CLL = chronic lymphocytic leukemia
Monitor
- neurologic assessment every 8 hours
Adverse effects
- cytokine release syndrome (cytokine storm)* most common
- CAR T-cell-related encephalopathy (CRES) 2nd most common
- may result in fatal cerebral edema[4]
- may result from reactivation of herpesvirus 6B[19]
Laboratory
- daily starting day of infusion
Procedure
- a tumor-binding element is introduced into a patient's T-cells using viral vectors
- these T-cells are cultured to produce large numbers of such cells, then reinfused into the patient
- modified T-cells attack leukemia cells with CD19 antigen (B-cells) or CD7 antigen (T-cells)
- BCMA target in multiple myeloma[10]
*
- vaccinations
- CAR T-cell therapy directed against B-cell antigens (CD19/BCMA)[21]
- patients should not receive influenza vaccine & COVID-19 vaccine < 3 months after completing therapy
- non-live vaccines should not be given < 6 months after completing therapy
- CAR T-cell therapy directed against B-cell antigens (CD19/BCMA)[21]
Clinical trials
- relapsed B-cell acute lymphoblastic leukemia (ALL)
- relapsed or refractory T-cell acute lymphoblastic leukemia
- complete response in 90% of patients in phase 1 trial[17]
Notes
More general terms
More specific terms
- afamitresgene autoleucel (Tecelra)
- axicabtagene ciloleucel (Yescarta)
- brexucabtagene autoleucel (Tecartus, Zynteglo)
- ciltacabtagene autoleucel (Carvykti)
- idecabtagene vicleucel (Abecma)
- lifileucel (Amtagvi)
- lisocabtagene maraleuce (BREYANZI)
- obecabtagene autoleucel (obe-cel)
- tisagenlecleucel; CTL019 (Kymriah)
References
- ↑ Komaroff AL Immunotherapy to Fight Cancer Begins to Work. NEJM Journal Watch. June 16, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
- ↑ Gever J FDA Approves CAR T-Cell Therapy for Leukemia. 'First gene therapy available in the United States,' says agency. MedPage Today. August 30, 2017 https://www.medpagetoday.com/HematologyOncology/Leukemia/67615
FDA News Release. Aug 30, 2017 FDA approval brings first gene therapy to the United States. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm - ↑ Court E Novartis' CAR-T gene therapy, the first approved by FDA, to cost $475,000 MarketWatch. Aug 31, 2017 http://www.marketwatch.com/story/novartis-car-t-gene-therapy-the-first-approved-by-fda-to-be-priced-based-on-cancer-patients-outcomes-2017-08-30
- ↑ 4.0 4.1 Anello J, Feinberg B, Heinegg J et. al. New Guidelines and Recommendations, October 2017 Medscape - Oct 06, 2017 http://reference.medscape.com/viewarticle/886616_5
- ↑ Kuehn B The Promise and Challenges of CAR-T Gene Therapy. JAMA. Published online November 22, 2017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29167891 https://jamanetwork.com/journals/jama/fullarticle/2664338
- ↑ Wikipedia: Tisagenlecleucel https://en.wikipedia.org/wiki/Tisagenlecleucel
- ↑ 7.0 7.1 Schuster SJ, Svoboda J, Chong EA Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. Dec 10, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29226764 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1708566
Tran E, Longo DL, Urba WJ A Milestone for CAR T Cells N Engl J Med. Dec 10, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29226781 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1714680 - ↑ Young K, Fairchild DG, Di Francesco L. Physician's First Watch, Jan 31, 2018 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
American Society of Clinical Oncology, News Release Jan 30, 2018 CAR T-Cell Immunotherapy Named Advance of the Year in Annual ASCO Report. Cancer Progress Report Highlights Life-Saving Potential of Immunotherapy, Critical Role of Federal Funding. https://www.asco.org/about-asco/press-center/news-releases/car-t-cell-immunotherapy-named-advance-year-annual-asco-report
American Society of Clinical Oncology Clinical Cancer Advances 2018 ASCO's 13th Annual Report on Progress Against Cancer. https://www.asco.org/research-progress/reports-studies/clinical-cancer-advances-2018 - ↑ 9.0 9.1 Park JH, Riviere I, Gonen M et al Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N Engl J Med 2018; 378:449-459. Feb 1, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29385376 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1709919
- ↑ 10.0 10.1 10.2 Fuerst ML CAR T-Cell Therapy Shows Durable Activity in Heavily Pretreated Multiple Myeloma. B-cell maturation antigen most promising myeloma target for CAR T-cell therapy. MedPage Today. ASCO Reading Room. Feb 1, 2018 https://www.medpagetoday.com/reading-room/asco/immunotherapy/70885
Cohen AD, Garfall AL, Stadtmauer EA et al 505 Safety and Efficacy of B-Cell Maturation Antigen (BCMA)- Specific Chimeric Antigen Receptor T Cells (CART-BCMA) with Cyclophosphamide Conditioning for Refractory Multiple Myeloma (MM). ASH 59th Annual Meeting. Dec 9-12, 2017 https://ash.confex.com/ash/2017/webprogram/Paper106279.html - ↑ 11.0 11.1 Nelson R T-Cell Biomarker Predicts Response to CAR T-Cell Therapy in Patients With CLL Medscape - May 07, 2018. https://www.medscape.com/viewarticle/896261
Fraietta JA, Lacey SF, Orlando EJ et al Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nature Medicine. April 30, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29713085 https://www.nature.com/articles/s41591-018-0010-1.epdf - ↑ 12.0 12.1 Schuster SJ, Bishop MR, Tam CS et al Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. Dec 1, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30501490 https://www.nejm.org/doi/full/10.1056/NEJMoa1804980?query=featured_home
- ↑ 13.0 13.1 13.2 Bankhead C CAR T-Cell Responses Prove Durable in ALL, DLBCL. Two studies demonstrate long-term control in relapsed/refractory disease. MedPage Today. Dec 1, 2018 https://www.medpagetoday.com/meetingcoverage/ashhematology/76644
Grupp SA, et al Updated analysis of the efficacy and sasfety of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia. American Society of Hematology (ASH) 2018; Abstract 895.
Schuster SJ, et al Sustained disease control for adult patients with relapsed or refractory diffuse large B-cell lymphomas: An updated analysis of JULIET, a global pivotal phase II trial of tisagenlecleucel. American Society of Hematology (ASH) 2018; Abstract 1684. - ↑ Jacobson C, Emmert A, Rosenthal MB CAR T-Cell TherapyA Microcosm for the Challenges Ahead in Medicare. JAMA. Published online July 29, 2019. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31355862 https://jamanetwork.com/journals/jama/fullarticle/2744409
- ↑ 15.0 15.1 Young YD Medicare Announces Coverage for CAR T-Cell Therapy Medscape - Aug 08, 2019. https://www.medscape.com/viewarticle/916604
- ↑ Liu E, Marin D, Banerjee P et al Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med 2020; 382:545-553. Feb 6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32023374 https://www.nejm.org/doi/full/10.1056/NEJMoa1910607
- ↑ 17.0 17.1 17.2 Bankhead C Anti-CD7 CAR-T Therapy Yields High Response Rate in Acute Leukemia. Complete responses in 18 of 20 patients with relapsed/refractory T-cell ALL. MedPage Today August 4, 2021 https://www.medpagetoday.com/hematologyoncology/leukemia/93902
Pan J, Tan Y, Wang G et al Donor-derived CD7 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia: First-in-human, phase I trial. J Clin Oncol. 2021. Jul 29 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34324392 https://ascopubs.org/doi/abs/10.1200/JCO.21.00389 - ↑ 18.0 18.1 Mackensen A et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 2022 Oct; 28:2124. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36109639 https://www.nature.com/articles/s41591-022-02017-5
- ↑ 19.0 19.1 Lareau CA, Yin Y, Maurer K et al. Latent human herpesvirus 6 is reactivated in CAR T cells. Nature 2023 Nov; 623:608 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37938768 https://www.nature.com/articles/s41586-023-06704-2
- ↑ 20.0 20.1 Amor C, Fernandez-Maestre I, Chowdhury S et al Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nat Aging. 2024 Jan 24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38267706 https://www.nature.com/articles/s43587-023-00560-5
- ↑ 21.0 21.1 Brooks M ASCO Releases Vaccination Guidelines for Adults With Cancer MDedge/Internal Medicine. March 28, 2024 https://www.mdedge.com/internalmedicine/article/268479/preventive-care/asco-releases-vaccination-guidelines-adults-cancer