Last spring, MUSC Health became the only center in South Carolina and one of a handful of medical centers in the Southeast certified to offer chimeric antigen receptor T-cell (CAR-T) therapy, the first FDA-approved gene transfer-based immunotherapy for refractory or relapsed B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL).
B-cell ALL and NHL are blood cancers affecting B lymphocytes, a type of white blood cell that marks foreign invaders for destruction by T cells. ALL originates in the bone marrow and is the most common childhood cancer, while NHL originates in the lymphatic system and is the seventh most common cancer in adults.1,2 Both cancers have high cure rates with traditional treatments, such as chemotherapy, radiation and bone marrow transplant (80-90% for ALL, 71% for NHL). However, for patients with refractory cancers that do not respond to traditional therapies or who relapse after receiving these therapies, there have been no further treatment options, making the advent of CAR-T therapy an important step.
“CAR-T therapy is a way of harnessing someone’s own immune system and reprogramming it to fight against the cancer,” explains Michelle P. Hudspeth, M.D., associate professor of pediatrics and director of the Blood & Marrow Transplant (BMT) Program at the MUSC Hollings Cancer Center.
To do this, T cells are collected from the patient and sent to a laboratory, where the cells are engineered to carry a chimeric antigen receptor (CAR) gene. This gene reprograms the T cells to make CARs that bind a specific B-cell marker, CD19, thereby enabling the patient’s own T cells to recognize and kill B cells. The T cells are then infused back into the patient and act as a “living drug.” In clinical trials, CAR-T therapy demonstrated complete remission rates of over 50%.3,4
At MUSC, turning the science fiction-like promise of CAR-T therapy into a treatment reality involved monumental efforts in collaboration. Once CAR-T therapy received FDA approval, MUSC’s BMT team successfully completed onboarding of the treatment for children and young adults (up to 25 years old) with refractory or relapsed B-cell ALL.
“It really speaks to resources across the university, from the clinical trials office, pharmacy, nurses, finance and emergency departments, inpatient and outpatient units, to the intensive care unit (ICU) and cancer staff,” says Hudspeth. “This level of engagement shows one of MUSC’s main strengths, and that’s collaboration and the willingness to push things forward to provide the best therapies for patients.”
From the patient’s standpoint, receiving CAR-T therapy involves typical outpatient and inpatient stays and consists of a leukapheresis procedure to collect white blood cells, chemotherapy to prepare the body for CAR-T therapy, and infusion of CAR-T cells. The routine nature of the treatment experience underscores the BMT team’s expert choreography behind the scenes.
According to Hudspeth, “there are a million and one safety checks involving two very specialized teams: the hemapheresis team that collects the patient’s T cells and the cryopreservation team that handles the CAR-T cells for infusing back into the patient.”
After receiving CAR-T therapy, patients remain in the hospital for monitoring of both the treatment response and potential side effects, such as the loss of healthy B cells and a dangerous inflammatory condition called cytokine release syndrome (CRS). Fortunately, standby treatments are in place, including anticytokine therapy for CRS.
“There are very precise CRS treatment algorithms,” says Hudspeth. “At any point a patient may have their first encounter, our staff has been trained to recognize, communicate, understand and follow the treatment protocols. So far, we’ve treated our first patient, and we’re pleased that he didn’t have toxicity, side effects or require ICU care.”
As part of the Children’s Oncology Group, MUSC has also been selected as a site for a clinical trial that will test CAR-T therapy as a frontline treatment for B-cell ALL patients at high risk for relapse with traditional therapy. In this trial, patients undergoing chemotherapy who show signs of cancer after just two treatment cycles will be switched to CAR-T therapy, with the medication provided at no cost to patients.
“We are excited to offer this less toxic treatment earlier in therapy,” says Jennifer J. Jaroscak, M.D., an associate professor of pediatric hematology and oncology at MUSC. “Treating highrisk B-cell ALL up front with CAR-T therapy has the potential to significantly reduce the length of treatment for patients, from the standard two and a half years down to four months.”
Because of the personalized and engineered nature of CAR-T therapy, one challenge that the U.S. health care system must overcome is the prohibitive cost — the latest estimates suggest a hefty price tag of $475,000.5
“Just like any other significant therapy, medical as well as financial eligibility must be determined,” cautions Hudspeth. “It takes extensive effort from our financial group to work out a case-by-case negotiation agreement with insurance companies and Medicaid to offer these new therapies in a responsible way.”
Despite the financial hurdles, the possibilities for CAR-T therapies seem endless. At MUSC, under the lead of Brian Hess, M.D., assistant professor of medicine, onboarding of CAR-T therapy for adults with NHL is well under way, and recruitment for the CAR-T therapy clinical trial for high-risk B-cell ALL will begin this fall. On a larger scale, the frontiers of CAR-T technology are also expanding. Scientists are testing this technology on solid cancers, which are more prevalent than blood cancers, and developing second-generation CAR-T cells that attack more than just the CD19 marker to prevent relapse.6,7
“It’s been a lot to work through, but we’re excited,” says Hudspeth. “CAR-T therapy represents a revolutionary way to be able to potentially cure patients who were once incurable.”
1. American Cancer Society. https://www.cancer.org/cancer/acute-lymphocyticleukemia/about/what-is-all.html.
2. American Cancer Society. https://www.cancer.org/cancer/non-hodgkin-lymphoma.html.
3. Ronson A, et al. Curr Oncol Rep. 2016;18(6):39. doi:10.1007/s11912-016-0519-8.
4. Neelapu SS, et al. N Engl J Med. 2017;377(26):2531-2544. doi:10.1056/NEJMoa1707447.
5. Hay AE, Cheung MC. J Med Econ. 2019;22(7): 613-615. doi:10.1080/13696998.2019.1582059.
6. Schmidts A, Maus MV. Front Immunol. 2018;9:2593. doi:10.3389/fimmu.2018.02593.
7.Townsend MH, et al. J Exp Clin Cancer Res. 2018;37(1):163. doi:10.1186/s13046-018-0817-0.