By Jim Kesslick
For decades, cancer therapy comprised the standard triad of surgery, chemotherapy, and radiation. Recently, however, immunotherapy―the harnessing of a patient’s own immune system to attack cancerous cells―has emerged as a potentially lifesaving option for some patients who don’t respond to standard cancer therapy. As wondrous as this new therapy may be, it’s important to approach training and education about it in a balanced way. In this blog, I explore CAR-T therapy as an example of how it’s done.
An immunotherapy dubbed CAR-T―for chimeric antigen receptor T cell―has garnered considerable attention as “cancer’s newest miracle cure” because of its remarkable efficacy in treating certain forms of blood cancers.1 Due to its potentially transformative impact, CAR-T therapy was named the 2018 advance of the year in cancer treatment by the American Society of Clinical Oncology.2
CAR-T represents a major paradigm shift in the approach to cancer therapy. According to Renier J. Brentjens, MD, PhD, of the Memorial Sloan Kettering Cancer Institute and an early pioneer in CAR-T development, CAR-T therapy is the same as “giving patients a living drug.”3 CAR-T development involves a series of complex steps in which the patient’s own T cells―one of the most important and effective white blood cell types in the immune system―are genetically redesigned to attack specific proteins called antigens that predominate on the surface of certain cancer cells.
CAR-T therapies can yield long-term―even lifelong―benefits after a single administration. Normally, when T cells target harmful invaders the first time, they are reprogrammed to remember these invaders the second time around and thereafter. CAR-T cells act similarly and, as a result, their activity against a specific cancer cell can persist for a patient’s lifetime.4
Thus far, commercially available CAR-T therapies only target the CD19 antigen protein that is overexpressed on the malignant B cells characteristic of blood cancers such as lymphoblastic leukemia and lymphoma. New CAR-T antigen targets are under active investigation for these blood cancers.5,6
In clinical studies, CAR-T therapy has demonstrated efficacy in treatment-resistant forms of the most common childhood cancer, acute lymphoblastic leukemia (ALL).4,7 Although the vast majority of children with ALL will be successfully treated with standard cancer therapy, relapsing cancer occurs in almost 20%. Clinical studies have shown that in these hard-to-treat patients, CAR-T therapy yields significant long-term efficacy, eliminating signs of cancer in up to 90% of patients. Moreover, in adults with advanced, intractable lymphoma, CAR-T therapy impressively eliminated all signs of cancer in approximately half of patients.3,8
Therapeutic and Access Limitations
Similar to other cancer therapies, CAR-T cell therapy is not free of side effects. The most frequent and troublesome side effect is cytokine release syndrome (CRS).3 As part of normal activity, T cells release chemical messengers called cytokines that can cause a strong inflammatory response in the body. A massive infusion of CAR-T cells as part of the normal therapeutic regimen can result in a sudden, prolonged, and on occasion, life-threatening elevation in cytokines characteristic of CRS. This reaction can result in fever, malaise, fatigue, and muscle aches, and potentially fatal cardiac disturbances and organ failure.9
In many cases CRS can be constrained with therapies such as steroids, or in severe cases, tocilizumab, a treatment that blocks the action of the inflammatory cytokine IL-6.3 Because of the risks for CRS and associated neurological problems, CAR-T must be administered at specialized centers with properly trained staff with access to tocilizumab.3,4
Another challenge is that currently available CAR-T therapies don’t focus exclusively on malignant cells: the main antigenic target of the two currently available CAR-T therapies, the CD19 protein, is also present on normal B cells. As a consequence, CAR-T therapy can result in widespread depletion of normal B cells―called B-cell aplasia―resulting in a reduced ability to fight infection. To overcome this deficit, many patients undergoing CAR-T therapy receive immunoglobulin treatment.3
In addition to these clinical hurdles, CAR-T therapy comes with a high price tag—even by today’s standards. The upfront cost is approximately $400,000 for each treatment. This cost does not include the management and treatment of serious side effects that may lead to hospitalization. With those factored in, actual treatment costs can exceed $1 million per patient.10
CAR-T therapy is covered by most commercial insurers on an individual basis; however, Medicaid and Medicare coverage may be more problematic. Some Medicaid programs deny coverage for CAR-T therapy categorically and Medicare coverage for inpatient administration is still evolving.
Communicating About CAR-T
CAR-T therapy has produced stunning and sometimes lifesaving results in some patients with treatment-resistant blood cancers and deserves recognition as a breakthrough paradigm for cancer management. But in medical communications and training, we must offer a balanced approach that focuses on its real world limitations as well.
In addition to conveying the mechanism of action and clinical benefits of CAR-T, any communications and training should address factors that may temper its use such as:
- Who are the appropriate patients for this therapy?
- What side effects might limit use?
- How might cost impact patient and insurance provider acceptance?
It should be clearly communicated that CAR-T therapy is indicated for only a relatively narrow slice of the cancer population―patients with certain treatment-resistant blood cancers―and that this form of immunotherapy is associated with potentially significant issues related to side effects and cost.
By providing a balanced perspective of CAR-T therapy, you’ll leave your audience with a more accurate appraisal of the benefits and potential limitations as well as an idea of how this clinical advancement will realistically fit in the overall approach to cancer management in coming years.
- Park A. Cancer’s newest medical cure. Time. http://time.com/4895010/cancers-newest-miracle-cure/. Published August 10, 2017. Accessed December 21, 2018.
- Guthrie G. CAR T-Cell Immunotherapy: The 2018 Advance of the Year. Cancer.Net. https://www.cancer.net/blog/2018-01/car-t-cell-immunotherapy-2018-advance-year. Published January 30, 2018. Accessed December 21, 2018.
- National Cancer Institute. CAR T cells: Engineering patients’ immune cells to treat their cancers. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells. Published December 14, 2017. Accessed December 21, 2018.
- Cancer Treatment Centers of America. Five things you should know about CAR T-cell therapy. https://www.cancercenter.com/discussions/blog/five-things-you-should-know-about-car-t-cell-therapy/. Published March 20, 2018. Accessed December 21, 2018.
- Fry TJ, Shah NN, Orentas RJ, et al. CD22-CAR T cells induce remission in CD19-CAR naïve or resistant B-ALL. Nat Med. 2018;24(1):20-28. doi: 10.1038/nm.4441.
- Berahovich R, Zhou H, Xu S, et al. CAR-T cells based on novel BCMA monoclonal antibody block multiple myeloma cell growth. Cancers (Basel). 2018;10(9). pii: E323. doi: 10.3390/cancers10090323.
- D’Aloia MM, Zizzari IG, Sacchetti B, Pierelli L, Alimandi M. CAR-T cells: the long and winding road to solid tumors. Cell Death Dis. 2018;9(3):282. doi: 10.1038/s41419-018-0278-6.
- Kochenderfer JN, Dudley ME, Kassim SH, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015;33(6):540-9. doi: 10.1200/JCO.2014.56.2025.
- Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics. 2016;3:16011. doi: 10.1038/mto.2016.11.
- Andrews M. Staggering prices slow insurers’ coverage of CAR-T cancer therapy. Kaiser Health News. http://www.philly.com/philly/health/staggering-prices-slow-insurers-coverage-of-car-t-cancer-therapy-20180717.html. Published July 17, 2018. Accessed on December 21, 2018.
Jim Kesslick has a master’s degree in experimental psychology with an emphasis on neurophysiology. His medical writing career includes 10 years at Johnson & Johnson and 15 years as a freelancer. Jim’s experience spans numerous therapeutic specialties and projects, including journal articles, monographs, abstracts, scripts, dossiers, sales trainings, and patient education materials. As a medical writer for Encompass, Jim has developed numerous high-quality sales training modules and video scripts.