“The FDA approval of (Tecartus) will change the way we treat patients with relapsed MCL forever and for the better,” said Dr. Michael Wang.
The Food and Drug Administration’s (FDA) recent approval of Tecartus (brexucabtagene autoleucel, formerly KTE-X19) for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) will forever change the way the disease is treated, according to Dr. Michael Wang.
“The FDA approval of (Tecartus) will change the way we treat patients with relapsed MCL forever and for the better,” Wang, a professor in the department of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center, said in an interview with CURE®’s sister publication, OncLive®.
With this approval, Tecartus became the first and only approved chimeric antigen receptor (CAR) T-cell therapy in this patient population.
The agency based its decision on data from the single-arm, open-label ZUMA-2 trial, which showed that 87% of patients responded to a single infusion of the CAR T-cell therapy. Sixty-two percent of those patients achieved a complete response after the infusion.
“In this study, patients had received three prior therapies, so (Tecartus) was the fourth therapy patients received,” said Wang, who is also the lead investigator for the ZUMA-2 trial. “In the fourth-line setting, generally the response rate is about 20% to 25%. With the CD19-directed CAR T-cell therapy, the response rate is 87%, and the (complete response) rate is 62%.”
Side Effect Profile
Among patients evaluable for safety, 18% experienced a serious or severe side effect of cytokine release syndrome (CRS) and 37% experienced serious or severe neurologic toxicities.
CRS and neurotoxicity were very well managed among the patient population in the ZUMA-2 trial, according to Wang, however, he did note that one patient died from CRS.
“Historically, we have always been concerned about CRS,” said Wang. “Patients can have a hard time with hypotension and high fevers. Now, we have so many therapies to support us, including early use of steroids such as (Actemra).”
Additionally, Wang acknowledged that there was one instance where a patient had a severe neurotoxicity and was treated with high-dose steroids as well as a ventriculostomy, which is when a hole is drilled into the cranium to allow pressure to escape. The ventriculostomy, along with another procedure, prevented brain swelling from occurring, according to Wang.
“We reversed it, and now the patient is in (complete response) at work without any residual neurotoxicity,” he said. “This is a remarkable example of CAR T-cell therapy toxicity management and prolonged efficacy.”
Very New Therapy
The use of CAR T-cell therapies are still relatively new in the field of MCL and researchers are still in the process of figuring things out, according to Wang.
“In the ZUMA-2 trial, we found that certain cytokines are associated with the efficacy and the toxicity of the product,” he said. “Therefore, we want to use different measures to enhance the efficacy and reduce the toxicity using cytokine and chemokine profiling.”
One thing Wang noted is that more research is needed to study minimal residual disease. He said that because there were only 60 patients included in the primary analysis of the trial, more samples will need to be studied in a controlled setting to better understand the relationship between cytokines, CRS and neurotoxicity.
“We also want to know how long CAR T cells can persist,” said Wang. “Some patients have CAR T-cell persistence one year after receiving therapy, but we want even longer timepoints.”
Additionally, Wang mentioned how researchers want to continue to follow the CAR T cells to see what exactly happens to them.
“It is a new but exciting and promising field,” he concluded. “My hope is that CAR T-cell therapy will cure a fraction of patients with MCL.”
A version of this story originally appeared on OncLive® as, “Wang Welcomes the FDA Approval of Brexucabtagene Autoleucel in MCL.”