CAR T: A New Treatment for Complex Cancer Cases
Mayo Clinic, a leader in clinical practice, education and research, joins multiple other medical facilities in research as well as clinical trials of a groundbreaking cancer treatment called chimeric antigen receptor T cell therapy (CAR T).
Yi Lin, M.D., a Mayo Clinic hematologist and the chair of the cellular therapeutic cross-disciplinary group at the Mayo Clinic Cancer Center, says she is excited about the potential of CAR T.
“This is really the first treatment of its kind that is coming to the market,” Dr. Lin says.
T cells are a type of white blood cell that circulates in the blood throughout the body. Their normal job is to scan for changes such as infection and cancer and get rid of them. Many cancers have found ways to suppress the T cells from doing this job. CAR T cell is one way to overcome that. To make CAR T cells, patients’ own T cells are collected and genetically treated in the lab to express CAR. These CARs are a fusion of different parts of naturally occurring receptors in T cells to enable the T cells to recognize an antigen (or marker) at the surface of cancer cells and activate T cells’ ability to kill these cancer cells.
Clinically, a patient undergoes a procedure called leukapheresis in which they are connected to a machine similar to blood donation process, and white blood cells are taken from their blood. These white blood cells are shipped to a lab where the T cells are genetically treated to become CAR T cells. The CAR T cells are shipped back to the treatment center. Patient then typically receives chemotherapy drugs that are dosed not with the intent of killing tumors but to prepare their immune system to receive the CAR T cells. After chemotherapy, patients receive infusion of their own CAR T cells by IV. In the first month after CAR T treatment, patients can experience side effects from the CAR T cells actively growing and killing cancer cells in their body. Some of these side effects are very different from the typical side effects seen with chemotherapy and stem cell transplant. These include cytokine release syndrome and neurologic events. During this period, close monitoring and supportive care at a treatment center familiar with CAR T treatment is necessary.
CAR T treatment requires special training and expertise: collecting blood cells and making CAR T cells, given CAR T treatment, and supportive care after CAR T treatment. Therefore it is not available at all medical centers. Currently in the US, this exciting, new and complex treatment is available in clinical trial testing at NCI and a number of major academic medical centers. Mayo Clinic has a number of clinical trials for CAR T therapy in B-ALL, non-Hodgkin lymphoma, and multiple myeloma.
Patient with cancers that has the antigen or marker that CAR T cells can recognize would be eligible. CAR T cells that target CD19, an antigen or marker that is on B-cell blood cancers such as B-cell acute lymphoblastic leukemia (B-ALL), B-cell non-Hodgkin lymphoma, and chronic lymphocytic leukemia have been tested the most in clinical trials to date. BCMA (B-cell maturation antigen) targeting CAR T is also showing early promise in multiple myeloma. There are a number of early phase clinical trials testing CAR T targeting antigens also seen in solid tumors.
The attraction of this treatment modality is that this is one way to boost the patient’s own immune system to fight their cancer. However, given that this is a very new treatment, long time follow-up is still needed to understand the potential long-term risks with this treatment. (FDA currently requires 15 years of follow-up for patients who have received CAR T treatment.)
On July 12, 2017, the Oncology Drug Advisory Committee (ODAC) reviewed data from clinical trial with Tisagenlecleucel (CTL019, CD19 target CAR T, Novartis) for pediatric and young adults with relapsed, refractory B-ALL and unanimously voted to recommend approval by FDA. This is a landmark review for the first treatment of its kind, according to Dr. Lin. Dr. Lin says FDA approval is anticipated in the next few months and will bring on a new era for cellular immunotherapy in the clinic. In that study, 63 patients were treated with Tsiagenlecleucel, 52 patients achieved complete remission (overall response rate 83%). This is remarkably high response rate compared to other clinically available treatments.
In adults with relapsed or refractory non-Hodgkin lymphoma, Kite Pharma has submitted their clinical trial data with Axicabtagene Ciloleucel (axi-cel, KTE-C19) to the FDA, and review is anticipated later this year. In their phase II study, 101 patients were treated, with 82% overall response rate, and 54% complete response. The complete response rate is approximately several times higher than the typical responses seen in similar patient population who have received other types of clinically available treatments, according to Dr. Lin.
In multiple myeloma, BCMA targeting CAR T (bb2121) from a multi-center phase I trial conducted by BlueBird Bio is showing 89% overall response rate for all treated patients, and 100% response rate for all patients treated above the first dose cohort. A couple of trials in myeloma did not show the same level of response and had higher incidence of more severe side effects, indicating that there are many aspects of CAR T treatments that are not yet understood and require more studies.
Mayo Clinic is also preparing to offer CAR T treatment when it becomes clinically available in the near future and has a pipeline of clinical trials to examine innovations to make CAR T treatments better, Dr. Lin says.
“Mayo Clinic has a long history of dedication to provide the best care possible for patients receiving complex treatments. CAR T therapy is the next era of new, complex but exciting cancer treatment that we will excel at and provide for our patients.”