FDA approves first CAR T-cell therapy for patients with mantle cell lymphoma

The U.S. Food and Drug Administration granted accelerated approval for brexucabtagene autoleucel (TECARTUS™, formerly KTE-X19) as the first and only CAR T-cell therapy for patients with mantle cell lymphoma (MCL) relapsed or refractory to prior treatments.

Investigators from Hackensack Meridian John Theurer Cancer Center (JTCC) at Hackensack University Medical Center in New Jersey participated in the pivotal trial which the approval was based: the ZUMA-2 clinical trial, which assessed the safety and effectiveness of brexucabtagene autoleucel in patients with relapsed or refractory MCL who had received up to five prior regimens of treatment and had exhausted all other therapies.

That transformative study showed that 93% of patients responded to treatment, with 67% achieving a complete response (no evidence of disease). The data were published in the April 2, 2020 issue of the New England Journal of Medicine.

MCL is an aggressive form of non-Hodgkin lymphoma that is very challenging to treat: patients typically respond to initial therapy but almost inevitably relapse and become resistant to therapy over time with then very poor outcome.

"The overall response rate (93%) particularly complete response (no evidence of disease) seen in over 2/3 of patients is unprecedented in that setting. In addition, though the follow up is short, over 75% of the complete responders were still in response at 12 months. Furthermore, among a subset of patients tested for minimal residual disease (83%) had no detectable residual disease," said Andre Goy, M.D., M.S., chairman and director of JTCC, Lymphoma Division chief, physician-in-chief of the Hackensack Meridian Health Oncology Care Transformation Service, and a renowned lymphoma expert who led JTCC's participation in the pioneering ZUMA-2 study.

The enthusiasm generated by this study during our presentation at ASH was palpable among providers; I am sure they are now ecstatic to be able to offer this game-changing treatment for a group of patients really in need."

Andre Goy, MD., MS., Chairman and Director, John Theurer Cancer Center, Hackensack University Medical Center

CAR T-cell therapy is a form of treatment which involves removing white blood cells called T cells from the patient, modifying them in the laboratory to train them to see a protein (CD19) on lymphoma cells, and then multiplying them to much larger numbers.

When given back to the patient intravenously, they expand further, identifying and killing cancer cells anywhere in the body.

Two other forms of CAR T-cell therapy -; axi-cell (Yescarta^®) and tisa-cell (Kymriah^®) -; were previously approved by the U.S. Food and Drug Administration to treat recurrent and persistent B-cell lymphoma in adults, as well as acute lymphoblastic leukemia in children and young adults up to age 25. Brexucabtagene autoleucel is the first CAR T-cell therapy approved to treat patients with MCL.

"John Theurer Cancer Center has long been a leading center for the research and treatment of lymphoma, and Hackensack Meridian Health is proud to have been involved in research leading to the approval of CAR T-cell therapy for mantle cell lymphoma," said Ihor Sawczuk, MD, FACS, president, Northern Region, and chief research officer, Hackensack Meridian Health.

"It is another example of our commitment to advancing cancer care through clinical research and offering the latest and most effective therapies to our patients based on those studies."

The ZUMA-2 study included people with MCL whose cancer came back or continued to grow despite having previously received chemoimmunotherapy and drugs called BTK inhibitors, such as ibrutinib or acalabrutinib.

After a single infusion of brexucabtagene autoleucel, 93% of patients experienced a reduction in their cancer and 67% achieved a complete response. These findings persisted regardless of the number of prior therapies or the extent of a patient's disease.

Notably, 40% of patients who initially had a partial response or stable disease (no reduction in cancer, but also no growth) went on to achieve a complete response within 3 to 12 months of the infusion.

Moreover, the patients' responses were also durable. At one year, estimated progression-free survival (the time before the cancer continues to grow) and overall survival were 61% and 83%, respectively. After a median follow-up of 12.3 months, 57% of patients remained in remission.

For the first 28 patients who were treated with KTE-X19) and had the longest follow-up time (median 27 months), 43% of the responders remained in remission -; a rate totally unprecedented for this population of patients.

"We have maintained a longstanding commitment to providing the most advanced cancer treatments to our community," said Mark D. Sparta, FACHE, president and chief hospital executive, Hackensack University Medical Center and executive vice president of Population Health, Hackensack Meridian Health.

"John Theurer Cancer Center was the first in New Jersey to be certified to offer CAR T-cell therapy and was involved in research evaluating its use long before its first FDA approval."

"We are honored to have been involved in its evaluation for patients with mantle cell lymphoma, who had no other treatment options once they had exhausted standard therapies."

Side effects of treatment were generally manageable and as expected with CAR T-cell therapy. These included cytokine release syndrome (a release of inflammatory proteins related to the immune response), low blood cell counts, and nervous system side effects -; all of which were reversible.