Overview of CAR T-cell therapy
T-cells are a type of white blood cells that play a crucial role in the immune system by targeting and eliminating infected cells and directing other immune responses.13 CAR T-cell therapy involves a process called apheresis, where blood is drawn from a vein and T-cells are separated from the blood.14 These T-cells are then engineered to add a new piece of genetic code, which creates chimeric antigen receptors (CARs). When the cells are infused back into a person’s body, they may be able to recognize and target cancer cells more effectively.1
In 2017, two CAR T-cell therapies received US Food and Drug Administration‘s (FDA) approval – one for patients up to 25 years old with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse,15 and the other for adults with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL).16
Since then, the CAR T-cell therapy landscape has expanded rapidly. Seven CAR T-cell therapies have been approved by the US FDA17,18,19,20,21,22,23 and six by the European Medicines Agency (EMA)24,25,26,27,28,29 and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA)30,31,32,33,34,35 to treat blood cancers, including ALL, LBCL, Mantle cell lymphoma (MCL), Follicular lymphoma (FL), Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM).36
In the near future, it is expected that CAR T-cell therapies may be approved in new and expanded indications in blood cancers and beyond. Today, there are hundreds of clinical trials underway to explore CAR T-cell therapies for other serious conditions, including solid tumor cancers, HIV and autoimmune diseases.37,38,39,40,41
It is estimated that more than
50,000 patients
have been treated to date with commercial CAR T-cell therapy
– many of whom would have likely had few, if any, other treatment options available with curative intent.35 CAR T-cell therapy has demonstrated its ability to induce prolonged remissions in patients with B-cell malignancies,42 and one of the earliest patients treated in clinical trials has experienced remission of more than a decade.43
Data have demonstrated long-term overall survival rates associated with CAR T-cell therapy.2,3,5,45,46,47,48,49 For those still alive at four years, it is possible that treatment with CAR T-cell therapy may be curative.50
As more patients are treated with CAR T-cell therapy across the world, our understanding of the treatment is also expanding. In one real-world study (n=551), the median overall survival with CAR T-cell therapy in older adults over 75 was observed to be comparable to those in younger patients.51 Real-world data showed that CAR T-cell therapy favorable responses and survival outcomes for patients with DLBCL were observed in both the second-line and third-line or later settings.52 Researchers understand much more about early predictors of safety profiles.53 The knowledge base is growing.
Unlike many other blood cancer therapies, CAR T-cell therapy is designed to be a one-time treatment. While not without its own side effects, for most patients, these side effects are generally reversible and time limited.54
Patients treated with CAR T-cell therapy often recover more quickly than those treated with standard of care, 55,56,57 due to time without symptoms of disease progression or treatment toxicities, thereby allowing for a faster return to their daily lives. 58
However, the nature of CAR T-cell therapies and the processes required for their manufacture and delivery, create challenges along the patient pathway that urgently need to be addressed.
References
1 National Cancer Institute. CAR T-cell therapy. Available online: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy
13 American Cancer Society. CAR T-cell Therapy and Its Side Effects. 2024. Available online: https://www.cancer.org/cancer/managing-cancer-treatment/types/immunotherapy/car-t-cell1.html
14 FDA. FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome. 2017. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisagenlecleucel-b-cell-all-and-tocilizumab-cytokine-release-syndrome
15 FDA. FDA approves axicabtagene ciloleucel for large B-cell lymphoma. 2017. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-large-b-cell-lymphoma
16 FDA Package Insert- tisagenlecleucel. 2024. Available online: https://www.novartis.com/usen/sites/novartis_us/files/kymriah.pdf
17 FDA Package Insert- axicabtagene ciloleucel. 2024. Available online: https://www.fda.gov/media/108377/download
18 FDA Package Insert- brexucabtagene autoleucel. 2024. Available online: https://www.fda.gov/media/140409/download
19 FDA Package Insert- lisocabtagene maraleucel. 2024. Available online: https://www.fda.gov/media/145711/download
20 FDA Package Insert- idecabtagene vicleucel. 2025. Available online: https://packageinserts.bms.com/pi/pi_abecma.pdf
21 FDA Package Insert- cilta-cel cabtagene autoleucel. 2024. Available online: https://www.fda.gov/media/156560/download
22 FDA Package Insert- obe-cel cabtagene autoleucel. 2024. Available online: https://www.fda.gov/media/183463/download
23 EMA Summary of product Characteristics-tisagenlecleucel. 2024. Available online: https://www.ema.europa.eu/en/documents/product-information/kymriah-epar-product-information_en.pdf
24 EMA Summary of product Characteristics-axicabtagene ciloleucel. 2024. Available online: https://www.ema.europa.eu/en/documents/product-information/yescarta-epar-product-information_en.pdf
25 EMA Summary of product Characteristics-brexucabtagene autoleucel. 2025. Available online: https://www.ema.europa.eu/en/documents/product-information/tecartus-epar-product-information_en.pdf
26 EMA Summary of product Characteristics-lisocabtagene maraleucel. 2024. Available online: https://www.ema.europa.eu/en/documents/product-information/breyanzi-epar-product-information_en.pdf
27 EMA Summary of product Characteristics-idecabtagene vicleucel. 2024. Available online: https://www.ema.europa.eu/en/documents/product-information/abecma-epar-product-information_en.pdf
28 EMA Summary of product Characteristics-ciltacabtagene autoleucel. 2025. Available online: https://www.ema.europa.eu/en/documents/product-information/carvykti-epar-product-information_en.pdf
29 MHRA Summary of Product Characteristics: axicabtagene ciloleucel. 2024. Available online: https://www.medicines.org.uk/emc/product/9493/smpc
30 MHRA Summary of Product Characteristics: tisagenlecleucel. 2024. Available online: https://mhraproducts4853.blob.core.windows.net/docs/7f7a601287e4f115f89bd473fffb9e91885b5c2
31 MHRA Summary of Product Characteristics: lisocabtagene maraleucel. 2024. Available online: https://mhraproducts4853.blob.core.windows.net/docs/2c868e1fa042193dc93d8167e2e9164e83b87e6
32 MHRA Summary of Product Characteristics. brexucabtagene autoleucel. 2025. Available online: https://mhraproducts4853.blob.core.windows.
net/docs/491a85cb9078bb88925ff650439e5e249f313453
33 MHRA Summary of Product Characteristics. Idecabtagene vicleucel. 2024. Available online: https://mhraproducts4853.blob.core.windows.net/
docs/20575242e44b0d5f7b12bbb409c576fa2a76b7d4
34 MHRA Summary of Product Characteristics: ciltacabtagene autoleucel. 2024. Available online: https://mhraproducts4853.blob.core.windows.net/docs/b346f06bc3ac727f18523d4257b2dacb749a32030
35 National Cancer Institute. CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers. 2025. Available online: https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
36 Ostrich MS, Lee CJ, Sobieski C, Weisdorf D, Couriel D. Access to CAR T-cell therapy: Focus on diversity, equity and inclusion. Blood Rev. 2024;63:101136.doi:10.1016/j.blre.2023.101136
37 Wang V, Gauthier M, Decot V, Rappepl L, Bensoussan E. Systematic Review on CAR-T Cell Clinical Trials Up to 2022: Academic Center Input. Cancers (Basel). 2023;15(4):1003. Published 2023 Feb 4. doi:10.3390/cancers15041003
38 Li YR, Lyu Z, Chen Y, Fang Y, Yang L. Frontiers in CAR-T cell therapy for autoimmune diseases. Trends Pharmacol Sci. 2024;45(9):839-857.doi:10.1016/j.tips.2024.07.005
39 Haghikia A, Schet G, Mougiakakos D. B cell-targeting chimeric antigen receptor T cells as an emerging therapy in neuroimmunological diseases. Lancet Neurol. 2024;23(6):615-624. doi:10.1016/S1474-4422(24)00140-6
40 Mao Y, Liao Q, Zhu Y, et al. Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open.label study. Cell Discov. 2024;10(1):49. Published 2024 May 14. doi:10.1038/s41421-024-00658-z
41 Cappell KM, Kochenderfer JN. Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol. 2023;20(6):359-371.doi:10.1038/s41571-023-00754-1
42 Children’s Hospital of Philadelphia. Emily Whitehead, First Pediatric Patient to Receive CAR T-Cell Therapy, Celebrates Cure 10 Years Later. 2022. Available online: https://www.chop.edu
43 Jaeger U, Bishop MR, Salles G. Myc Expression and Tumor-Infiltrating T Cells Are Associated with Response in Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL) Treated with Tisagenlecleucel in the Juliet Trial. Poster #1194. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition; December 5-8, 2020.
44 Westin JR, Oluwole OO, Kersten MJ, et al. Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma. N Engl J Med. 2023;389(2):148-157. doi:10.1056/NEJMoa2301665
45 Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel (liso-cel) vs standard of care (SOC) with salvage chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients (pts) with R/R large B-cell lymphoma (LBCL): 3-year follow-up (FU) from the randomized, phase 3 TRANSFORM study. J Clin Oncol. 2024;42(suppl 16):7013.
46 Mateos M-V, San-Miguel J, Dhakal, et al. Overall Survival (OS) with Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care (SoC) in Lenalidomide (Len)-Refractory Multiple Myeloma (MM): Phase 3 CARTITUDE-4 Study Update. Presented at: 2024 International Myeloma Society Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil. Abstract OA – 65.
47 Alawadhi S, Arnulf B, Patel K, et al. Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. Blood. 2024 Dec 5;144(23):2389-2401. doi:10.1182/blood.2022042582. PMID: 39197072.
48 National Cancer Institute. Trial Confirms CAR T-Cell Therapy Benefits People with Aggressive Lymphomas. July 10, 2023. Available online:
https://www.cancer.gov/news-events/cancer-currents-blog/2023/large-b-cell-lymphoma-axi-cel-zuma-7-trial
49 Chihara D, Liao L, Tkacz J, et al. Real-world experience of CAR T-cell therapy in older patients with relapsed/refractory diffuse large B-cell lymphoma. Blood. 2023;142(12):1047-1055. doi:10.1182/blood.2023020197
50 Rojek AE, Ahmed N, Gomez Llobell M, et al. CAR T cell therapy in early relapsed/refractory large B-cell lymphoma: real world analysis from the cell therapy consortium. Abstract #4503. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.
51 Strouse C, Fracco U, Shouval R et al. Predictors of Early Safety Outcomes with Axicabtagene Ciloleucel (axi-cel) in Patients with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL). Blood. 2024;144 (Supplement 1):609. https://doi.org/10.1182/blood-2024-207976
52 Mayo Clinic. Understanding CAR-T cell therapy and its potential side effects. 2023. Available online:
https://cancerblog.mayoclinic.org/2023/08/31/understanding-car-t-cell-therapy-and-its-potential-side-effects/
53 Cleveland Clinic. Top Myths About CAR T-Cell Therapy for Multiple Myeloma. 2025. Available online:
https://consultqd.clevelandclinic.org/top-myths-about-car-t-cell-therapy-for-multiple-myeloma
54 Sheykhhasan M, Manoochehri H, Dama P. Use of CAR T-cell for acute lymphoblastic leukemia (ALL) treatment: a review study. Cancer Gene Ther. 2022;29(8-9):1080-1096. doi:10.1038/s41417-021-00418-1
55 Elsawy M, Chavez JC, Aviv I, et al. Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma. Blood. 2022;140(21):2248-2260. doi:10.1182/blood.2022015478
56 Perthus A, Colin F, Charlton E, et al. Remission after CAR T-cell therapy: Do lymphoma patients recover a normal life? Hemasphere. 2024;8(5):e72. Published 2024 May 27. doi:10.1002/hema3.72
57 Perales MA, McGuirk JP, Fesen MR, et al. Real-World Treatment Patterns of Large B-Cell Lymphoma Patients over Time in a Post-CAR T
Approval Era. Transplant and Cell Ther. 2025;31(2):Supplement
58 Kourelis T, Bansal R, Patel KK, et al: Ethical challenges with CAR T slot allocation with idecabtagene vicleucel manufacturing access. J Clin
Oncol. 2022. 40(16):Supplement