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CAR T-cell therapy for Multiple Myeloma

By: Lyana Sayilar, PharmD Candidate c/o 2022

              Multiple myeloma is characterized by an accumulation of abnormal plasma cells in the bone marrow and the formation of tumors in bones. An insufficient quantity of healthy blood cells are produced in the bone marrow leading to a weakened immune system.1 The exact cause of multiple myeloma is unknown, but abnormalities of chromosomes and oncogenes; genes which can transform a normal cell into a tumor cell under certain conditions, may play a role. Idecabtagene vicleucel (Abecma®) is the first Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T-cell therapy for patients who have not responded to treatment or who experienced a relapse in multiple myeloma after four different treatment lines including an immunomodulatory agent, proteasome inhibitor, and an anti-CD38 monoclonal antibody.5 In order for patients to receive idecabtagene vicleucel, the benefits must outweigh the risks as outlined in the Risk Evaluation and Mitigation Strategy (REMS), a drug safety program who’s purpose is to ensure benefits outweigh risks in high-risk medications. 1

Idecabtagene vicleucel is a B-cell maturation antigen (BCMA)-directed genetically modified CAR T-cell therapy. 1 BCMA is expressed at high levels on malignant plasma cells. B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) are present and circulate at higher levels in patients with multiple myeloma, so they may induce downstream signaling cascades in multiple myeloma cells. APRIL and BAFF bind to BCMA on malignant plasma cells and induce the proliferation of multiple myeloma cells via activation of NF-kappa B and MAPK/JNK signaling pathway. 2,3 In addition, serum BCMA is present in greater quantities in patients with multiple myeloma  and can be used to monitor disease status in these patients. Therefore, targeting BCMA can be beneficial in treating multiple myeloma. 2 CAR T-cell therapy involves using a patient’s native, genetically modified T-cells, which are able to detect and kill specific cells. After T-cell modification, the patient’s T-cells are infused back into the patient. 1

Idecabtagene vicleucel is available as an IV suspension containing 460 million cells.7 Before administering idecabtagene vicleucel, thaw the infusion bag and administer within one hour of the start of thawing. If more than one IV bag is needed, complete the infusion of the first IV bag before thawing the second IV bag. Prior to its infusion, cyclophosphamide 300 mg/m2 IV and fludarabine 30 mg/m2 IV should be administered for three days. Cyclophosphamide and fludarabine should be given to decrease the number of T cells to make room for the new CAR T-cells, a process referred to as lymphodepletion.8 After two days of completing the chemotherapy, idecabtagene vicleucel infusion can be initiated. Approximately 30 to 60 minutes before infusion, acetaminophen 650 mg orally and diphenhydramine (12.5 mg IV or 25 to 50 mg orally) or another H1-antihistamine can be given to minimize the risk of infusion reactions. Once infused, rinse the tubing with 30-60 mL of 0.9% NaCl at the same rate as the infusion rate.4

Idecabtagene vicleucel does come with some limitations. It should not be administered to patients with an active infection or inflammatory disorder because life-threatening infections have occurred after the infusion. Its multiple black-boxed warnings include cytokine release syndrome (CRS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) (which results in decreased blood cell counts and an inflammatory reaction that attacks organs, such as the spleen and liver), neurologic toxicity, and prolonged cytopenia. CRS and HLH are a result of the activation and proliferation of T-cells, resulting in high fever and flu-like symptoms. Prior to idecabtagene vicleucel administration, at least two doses of 8 mg/kg tocilizumab IV should be prepared in case a CRS reaction occurs, as stated in the package insert which can be found on the FDA website.5 The most common side effects include cytokine release syndrome, infections, a weakened immune system, fatigue, and musculoskeletal pain. Side effects may be observed within one to two weeks after treatment or later. 1 Patients must be monitored at least daily for seven days. For four weeks following the infusion, patients should stay close to the healthcare facility in case side effects occur. For at least 8 weeks following the infusion, patients should be cautioned to avoid driving. 5

In conclusion, CAR T-cell therapy has been shown to be a useful approach in achieving a therapeutic response in patients with multiple myeloma and is being studied in other conditions, such as Human Immunodeficiency Virus (HIV). 6 Pharmacists should become familiar with CAR T-cell therapy and recognize the impact it can have on patients with refractory cancer, such as those with multiple myeloma. Staying informed about the many advancements in medicine such as this will allow for more efficient care for our patients.


  1. U.S. Food and Drug Administration. 2021. FDA Approves First Cell-Based Gene Therapy for Adult Patients with Multiple Myeloma. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-adult-patients-multiple-myeloma Accessed 1 October 2021.
  2. Tai, Y. and Anderson, K., 2015. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy, 7(11), pp.1187-1199. Accessed 1 October 2021
  3. Feng, D. and Sun, J., 2020. Overview of anti‐BCMA CAR‐T immunotherapy for multiple myeloma and relapsed/refractory multiple myeloma. Scandinavian Journal of Immunology, 92(2). Accessed 1 October 2021
  4. Medscape. 2021. Abecma (Idecabtagene vicleucel) dosing, indications, interactions, adverse effects, and more. https://reference.medscape.com/drug/abecma-idecabtagene-vicleucel-4000133#11. Accessed 1 October 2021.
  5. U.S. Food and Drug Administration. 2021. ABECMA. https://www.fda.gov/vaccines-blood-biologics/abecma-idecabtagene-vicleucel. Accessed 1 October 2021.
  6. Qi, J., Ding, C., Jiang, X. and Gao, Y., 2020. Advances in Developing CAR T-Cell Therapy for HIV Cure. Frontiers in Immunology, 11. Accessed 1 October 2021
  7. Idecabtagene Vicleucel. Lexi-Drugs. Hudson, OH: Lexicomp, 2021. http://online.lexi.com/. Updated August 27, 2021. Accessed October 1, 2021.
  8. Hoparx.org. https://www.hoparx.org/images/hopa/resource-library/patient-education/What-is_CAR-T-cell-therapy-CT-part1a.pdf. Accessed 9 October 2021.

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