Opinion: CAR T-Cell Therapy Remains a Promising Therapeutic Option Despite FDA Inquiry into Secondary Malignancies


Oncology nurses should be ready to offer informative guidance to patients and their families concerning the ongoing FDA inquiry and its potential impact.

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

For many patients and families facing the challenges of cancer, as well as the oncology nurses and providers dedicated to their care, CAR T-cell therapy has sparked a sense of optimism for the oncology treatment landscape.

CAR T-cell therapy is a form of immunotherapy which utilizes a patient’s own immune system to treat cancer.1 Cancer cells and other foreign substances in the body have proteins known as antigens on their surface. T cells and other immune system cells have proteins called receptors on their cell surface. These antigens and receptors fit together like a lock and key. Each antigen on a foreign cell has a unique immune receptor that will bind to it.2

The process of administering CAR T-cell therapy begins with the collection of the patient's T cells. These T cells are then modified in the laboratory, ensuring that their immune cells possess the appropriate receptors to bind to the correct antigens and effectively destroy the patient’s cancer cells. In the lab, engineers add a specific the gene for a specific receptor known as the Chimeric Antigen Receptor (CAR). The modified T cells are then reintroduced into the patient. CARs are specifically designed to target a particular type of cancer-associated antigen.2 These receptors are artificially created and do not occur naturally.1

There are currently 6 FDA-approved CAR T-cell therapies. Four of these target an antigen on cancer cells known as Cluster of Differentiation 19 (CD19), which is expressed by most B-cell malignancies—including diffuse large B-cell lymphoma and B cell acute lymphoblastic leukemia.3 The 4 CAR T-cell therapies targeting CD19 are lisocabtagene maraleucel (Breyanzi), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).4 The other 2 approved therapies target an antigen known as the B cell maturation antigen (BCMA), which is highly expressed in multiple myeloma.5 The 2 CAR T cell therapies targeting BCMA are idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti).4

Benefits of CAR T-Cell Therapy

The reason patients and oncology clinicians are so enthusiastic about CAR T-cell therapy is that individuals with relapsed and/or refractory hematologic malignancies can achieve impressive complete response rates with this treatment. In clinical trials, CAR T cells targeting CD19 were found to have complete response rates of up to 40% to 54% in patients with aggressive B cell lymphomas, 67% in patients with mantle cell lymphoma, and 69% to 74% in patients with indolent B cell lymphomas such as follicular lymphoma.5 Further, clinical trials with CAR T cells targeting BCMA have shown overall response rates of 73% to 98%.5

Risks of CAR T-Cell Therapy, Including the New FDA Investigation

Unfortunately, no cancer treatment is without potential adverse effects, and CAR T-cell therapy is no exception. CAR T-cell therapy is associated with Cytokine Release Syndrome (CRS), characterized by symptoms such as fever and hypotension, constituting an acute systemic inflammatory syndrome. Another potential side effect is Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), characterized by neurological effects such as altered mental status, hallucinations, speech changes, and seizures.1

In addition to the potential immediate side effects of CAR T-cell therapy, patients may also experience long-term side effects associated with the treatment. Since CAR T-cell therapy is a newer technology, information on long-term side effects is still being collected.6

The FDA has received reports of T-cell malignancies, including CAR-positive lymphoma, in patients treated with BCMA- or CD19-targeting CAR T-cell therapies. While the overall benefits of CAR T-cell therapy are still considered to outweigh the risks, the FDA is investigating the identified risk of T-cell malignancy. Patients treated with these therapies should undergo lifelong monitoring for new malignancies, and any new occurrences should be reported to the manufacturer for further evaluation. The potential risk of developing secondary malignancies is labeled as a class warning in the prescribing information for CAR T-cell therapy, and long-term safety studies are being conducted as part of post-marketing requirements.

Nursing Considerations

Patients who have received CAR T-cell therapy or are being evaluated for CAR T-cell therapy may inquire with their oncology team about the implications of the FDA investigation on their care. Oncology nurses can explain to patients that the FDA has stated that the benefits of CAR T-cell therapy are still considered to outweigh the risks at this time. Additionally, oncology nurses can discuss with their patients the importance of long-term follow-up to detect evidence of secondary malignancies.

Even in the age of frequent telemedicine visits, long-term follow-up appointments will still ideally occur in person, allowing patients to undergo both laboratory evaluation and physical exams to detect any abnormalities.

Patients should be educated to report any new symptom—such as fever, skin changes, enlarged lymph nodes, and bone pain—which may be indicative of secondary malignancy. Patients should be encouraged to report new symptoms promptly, rather than waiting for a future appointment.

In conclusion, in the dynamic field of cancer treatment, CAR T-cell therapy holds promise. Beyond FDA-approved therapies, CAR T-cell therapy is under investigation for other indications, including solid tumors. Although challenges associated with this therapy exist, like the reports of secondary malignancies, oncology nurses play a crucial role in keeping patients informed about the risks and benefits of this treatment and ensuring compliance with long-term follow-up.


  1. CAR T cells: Engineering immune cells to treat cancer. National Cancer Institute. March 10, 2022. Accessed December 4, 2023. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells.
  2. CAR T-cell therapy and its side effects. American Cancer Society. Accessed December 4, 2023. https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/car-t-cell1.html.
  3. Kochenderfer JN, Rosenberg SA. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol. 2013;10(5):267-276. doi:10.1038/nrclinonc.2013.46
  4. Chen YJ, Abila B, Mostafa Kamel Y. CAR-T: what is next? Cancers (Basel). 2023;15(3):663. Published 2023 Jan 21. doi:10.3390/cancers15030663
  5. 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
  6. U.S. Food and Drug Administration. FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies. November 28, 2023. Accessed December 4, 2023. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous
Recent Videos
Elizabeth Aronson
Shivani Gopalsami
Donna Catamero
Verina on Tackling Neurological Toxicities From CAR T-Cell Therapy
Sherry Adkins Talks Primary Care Provider Communication Following CAR T-cell Therapy
Gretchen McNally Speaks to the Role of Oncology Nurses in the Opioid Epidemic
Related Content
© 2024 MJH Life Sciences

All rights reserved.