The Pharmacist's Role in CAR-T Cell Therapy: From Protocol Development to Toxicity Reduction
Abstract
Background: CAR-T cell therapy is cutting-edge immunotherapy for hematologic malignancies, and the pharmacist has a crucial role to play in its safe delivery.
Aim: Through this review, the pharmacist's role in CAR-T therapy, ranging from protocol development to toxicity management, is evaluated with consideration of real-world evidence and the future direction.
Methods: A Systematic literature review was conducted on PubMed, Embase, and Web of Science using searches for studies between 2017–2025. Relevance to pharmacist roles in CAR-T therapy informed study selection, synthesizing data on protocol management, product handling, and toxicity mitigation.
Results: Pharmacists enable regulatory compliance, manage product logistics, and guide toxicity interventions, reducing adverse events by up to 40% in some settings. Case studies illustrate outpatient care (85% ambulatory care) and tocilizumab early start (90% severe CRS prevention). Complications are supply chain interruption and limited specialist roles (20% of centers).
Conclusion: Pharmacists are the key to the success of CAR-T therapy, improving safety and outcomes. Dedicated positions and standardized training would be necessary to cope with emerging challenges, especially in outpatient and solid tumor settings.
Full text article
References
Amini, L., Silbert, S. K., Maude, S. L., Nastoupil, L. J., Ramos, C. A., Brentjens, R. J., ... & Abou-el-Enein, M. (2022). Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion. Nature reviews Clinical oncology, 19(5), 342-355. https://doi.org/10.1038/s41571-022-00607-3
Awasthi, R., Maier, H. J., Zhang, J., & Lim, S. (2023). Kymriah®(tisagenlecleucel)–an overview of the clinical development journey of the first approved CAR-T therapy. Human vaccines & immunotherapeutics, 19(1), 2210046. https://doi.org/10.1080/21645515.2023.2210046
Benedetti, H., & Latchford, T. M. (2019). Developing BMT Nurses to Care for Axicabtogene Ciloleucel (Yescarta) Chimeric Antigen Receptor T Cell Patients. Biology of Blood and Marrow Transplantation, 25(3), S438-S439. https://doi.org/10.1016/j.bbmt.2018.12.474
Berdeja, J. G., Madduri, D., Usmani, S. Z., Jakubowiak, A., Agha, M., Cohen, A. D., ... & Jagannath, S. (2021). Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. The Lancet, 398(10297), 314-324. https://doi.org/10.1016/S0140-6736(21)00933-8
Black, A. (2018). Pharmacy Institutional Readiness for Marketed CAR-T Therapy: Checklists for Pharmacy Services.
Booth, J. P., Kusoski, C. L., & Kennerly-Shah, J. M. (2020). The pharmacist’s role in chimeric antigen receptor T cell therapy. Journal of Oncology Pharmacy Practice, 26(7), 1725-1731. https://doi.org/10.1177/1078155220948940
Brudno, J. N., & Kochenderfer, J. N. (2016). Toxicities of chimeric antigen receptor T cells: recognition and management. Blood, The Journal of the American Society of Hematology, 127(26), 3321-3330. https://doi.org/10.1182/blood-2016-04-703751
Dioverti, V., El Boghdadly, Z., Shahid, Z., Waghmare, A., Abidi, M. Z., Pergam, S., ... & Papanicolaou, G. A. (2022). Revised guidelines for coronavirus disease 19 management in hematopoietic cell transplantation and cellular therapy recipients (August 2022). Transplantation and Cellular Therapy, 28(12), 810-821. https://doi.org/10.1016/j.jtct.2022.09.002
Elsallab, M., & Maus, M. V. (2023). Expanding access to CAR T cell therapies through local manufacturing. Nature biotechnology, 41(12), 1698-1708. https://doi.org/10.1038/s41587-023-01981-8
Fala, L. (2018). Yescarta (Axicabtagene Ciloleucel) second CAR T-cell therapy approved for patients with certain types of large B-cell lymphoma.
Frey, N., & Porter, D. (2019). Cytokine release syndrome with chimeric antigen receptor T cell therapy. Biology of Blood and Marrow Transplantation, 25(4), e123-e127. https://doi.org/10.1016/j.bbmt.2018.12.756
Garfall, A. L., Dancy, E. K., Cohen, A. D., Hwang, W. T., Fraietta, J. A., Davis, M. M., ... & Melenhorst, J. J. (2019). T-cell phenotypes associated with effective CAR T-cell therapy in postinduction vs relapsed multiple myeloma. Blood advances, 3(19), 2812-2815. https://doi.org/10.1182/bloodadvances.2019000600
Geyer, M. B., Park, J. H., & Brentjens, R. J. (2018). Chimeric Antigen Receptor-T Cells for Leukemias in Adults: Methods, Data and Challenges. Cell and Gene Therapies, 75-92. https://doi.org/10.1007/978-3-319-54368-0_5
Giavridis, T., van der Stegen, S. J., Eyquem, J., Hamieh, M., Piersigilli, A., & Sadelain, M. (2018). CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nature medicine, 24(6), 731-738. https://doi.org/10.1038/s41591-018-0041-7
Iglesias-López, C., Agustí, A., Obach, M., & Vallano, A. (2019). Regulatory framework for advanced therapy medicinal products in Europe and United States. Frontiers in pharmacology, 10, 921. https://doi.org/10.3389/fphar.2019.00921
Jacobson, C. A., Locke, F. L., Ma, L., Asubonteng, J., Hu, Z. H., Siddiqi, T., ... & Pasquini, M. C. (2022). Real-world evidence of axicabtagene ciloleucel for the treatment of large B cell lymphoma in the United States. Transplantation and cellular therapy, 28(9), 581-e1. https://doi.org/10.1016/j.jtct.2022.05.026
June, C. H., O’Connor, R. S., Kawalekar, O. U., Ghassemi, S., & Milone, M. C. (2018). CAR T cell immunotherapy for human cancer. Science, 359(6382), 1361-1365. https://doi.org/10.1126/science.aar6711
Kamisetti, R. R. (2023). Strategies Followed for the Assessment of the Advanced Therapies by European Medicines Agency. DOI: 10.37421/2165-7920.2023.13.1569
Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., ... & Mackall, C. L. (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood, The Journal of the American Society of Hematology, 124(2), 188-195. https://doi.org/10.1182/blood-2014-05-552729
Lee, D. W., Santomasso, B. D., Locke, F. L., Ghobadi, A., Turtle, C. J., Brudno, J. N., ... & Neelapu, S. S. (2019). ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biology of blood and marrow transplantation, 25(4), 625-638. https://doi.org/10.1016/j.bbmt.2018.12.758
Locke, F. L., Miklos, D. B., Jacobson, C. A., Perales, M. A., Kersten, M. J., Oluwole, O. O., ... & Westin, J. R. (2022). Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. New England Journal of Medicine, 386(7), 640-654. DOI: 10.1056/NEJMoa2116133
Mahmoudjafari, Z., Hawks, K. G., Hsieh, A. A., Plesca, D., Gatwood, K. S., & Culos, K. A. (2019). American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group survey on chimeric antigen receptor T cell therapy administrative, logistic, and toxicity management practices in the United States. Biology of Blood and Marrow Transplantation, 25(1), 26-33. https://doi.org/10.1016/j.bbmt.2018.09.024
Marzal-Alfaro, M. B., Escudero-Vilaplana, V., Revuelta-Herrero, J. L., Collado-Borrell, R., Herranz-Alonso, A., & Sanjurjo-Saez, M. (2021). Chimeric antigen receptor T cell therapy management and safety: a practical tool from a multidisciplinary team perspective. Frontiers in oncology, 11, 636068. https://doi.org/10.3389/fonc.2021.636068
Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., ... & Grupp, S. A. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine, 378(5), 439-448. DOI: 10.1056/NEJMoa1709866
Mohty, R., Moreno Vanegas, Y., Chavez, J. C., & Kharfan-Dabaja, M. A. (2023). Lisocabtagene maraleucel for relapsed or refractory large B-cell non-Hodgkin lymphoma. Expert Review of Anticancer Therapy, 23(2), 121-126. https://doi.org/10.1080/14737140.2023.2171397
Moreno-Martínez, M. E., Vinent-Genestar, J., Muñoz-Sánchez, C., & Carreras-Soler, M. J. (2020). Hospital pharmacist's roles and responsibilities with CAR-T medicines. Farmacia Hospitalaria, 44(1), 26-31. https://doi.org/10.7399/fh.11333
Neelapu, S. S., Locke, F. L., Bartlett, N. L., Lekakis, L. J., Miklos, D. B., Jacobson, C. A., ... & Go, W. Y. (2017). Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. New England Journal of Medicine, 377(26), 2531-2544. DOI: 10.1056/NEJMoa1707447
Neelapu, S. S., Tummala, S., Kebriaei, P., Wierda, W., Gutierrez, C., Locke, F. L., ... & Shpall, E. J. (2018). Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nature reviews Clinical oncology, 15(1), 47-62. https://doi.org/10.1038/nrclinonc.2017.148
Nezvalova-Henriksen, K., Langebrake, C., Bauters, T., Moreno-Martinez, M. E., Ahnfelt, E., Ekelund, H., ... & Tam, A. (2023). Implementation and operational management of marketed chimeric antigen receptor T cell (CAR-T Cell) therapy—a guidance by the GoCART Coalition Pharmacist Working Group. Bone Marrow Transplantation, 58(10), 1069-1074. https://doi.org/10.1038/s41409-023-02072-7
Norelli, M., Camisa, B., Barbiera, G., Falcone, L., Purevdorj, A., Genua, M., ... & Bondanza, A. (2018). Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nature medicine, 24(6), 739-748. https://doi.org/10.1038/s41591-018-0036-4
Okamoto, S., Iida, M., Hamad, N., Duarte, F. B., Sureda, A., Srivastava, A., ... & European Society for Blood and Marrow Transplantation (EBMT. (2023). American Society of Transplantation and Cellular Therapy International Affair Committee: Report of the Third Workshop on Global Perspective to Access to Transplantation at the 2022 Tandem Meeting. Transplantation and Cellular Therapy, 29(7), 410-417. https://doi.org/10.1016/j.jtct.2023.02.024
Owusu, K. A., Schiffer, M., & Perreault, S. (2022). Chimeric antigen receptor T cells: Toxicity and management considerations. AACN Advanced Critical Care, 33(4), 301-307. https://doi.org/10.4037/aacnacc2022936
Parikh, R. H., & Lonial, S. (2023). Chimeric antigen receptor T‐cell therapy in multiple myeloma: a comprehensive review of current data and implications for clinical practice. CA: A Cancer Journal for Clinicians, 73(3), 275-285. https://doi.org/10.3322/caac.21771
Paroder, M., Le, N., Pham, H. P., & Thibodeaux, S. R. (2020). Important aspects of T‐cell collection by apheresis for manufacturing chimeric antigen receptor T cells. Advances in Cell and Gene Therapy, 3(1), e75. https://doi.org/10.1002/acg2.75
Perica, K., Curran, K. J., Brentjens, R. J., & Giralt, S. A. (2018). Building a CAR garage: preparing for the delivery of commercial CAR T cell products at Memorial Sloan Kettering Cancer Center. Biology of Blood and Marrow Transplantation, 24(6), 1135-1141. https://doi.org/10.1016/j.bbmt.2018.02.018
Salter, A. I., Pont, M. J., & Riddell, S. R. (2018). Chimeric antigen receptor–modified T cells: CD19 and the road beyond. Blood, The Journal of the American Society of Hematology, 131(24), 2621-2629. https://doi.org/10.1182/blood-2018-01-785840
Santomasso, B. D., Park, J. H., Salloum, D., Riviere, I., Flynn, J., Mead, E., ... & Brentjens, R. J. (2018). Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer discovery, 8(8), 958-971. https://doi.org/10.1158/2159-8290.CD-17-1319
Sterner, R. C., & Sterner, R. M. (2021). CAR-T cell therapy: current limitations and potential strategies. Blood cancer journal, 11(4), 69. https://doi.org/10.1038/s41408-021-00459-7
Authors
Copyright (c) 2025 Abdulrahman Atiah Alghamdi, Naif Ali Almalki, Fahad Mosakin Althubyani, Saleh Awadh Alshamrani, Manal Abdulaziz Alsharif, Eisi Menwer Alamri

This work is licensed under a Creative Commons Attribution 4.0 International License.