FDA Approves Tecartus for Relapsed/Refractory Acute Lymphoblastic Leukemia

The Food and Drug Administration (FDA) approved Tecartus (brexucabtagene autoleucel), a CAR-T cell therapy, for the treatment of adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL), according to Kite, a Gilead Company, the manufacturer of the agent.

“It’s a really powerful tool, and I’m really excited with all the data (from ZUMA-3) to bring it forward to patients and hopefully improve on what has not been great in terms of survival once patients relapse,” said Dr. Bijal D. Shah, associate member in the department in Malignant Hematology at the Moffitt Cancer Center, said in an interview with CURE®.

ZUMA-3 Shows Promise for Tecartus Treatment

Shah is the primary investigator of the ZUMA-3 clinical trial, whose results led to the approval of Tecartus for relapsed/refractory B-cell precursor ALL.

According to phase 2 data presented at the American Society of Clinical Oncology Annual Meeting, 31% of patients who responded to therapy on the ZUMA-3 were still responding at an average follow-up of 16.4 months – 97% of whom had a deep molecular remission, with no detectable amount of minimal residual disease.

Average overall survival was 18.2 months for all patients in the study, though for those who responded to Tecartus, researchers could not get an estimate on their average length of survival.

Sixty-five percent of patients achieved a complete response or with incomplete hematological recovery at an average follow-up of 12.3 months. However, the duration of complete response was estimated to exceed 12 months for more than half of the patients.

“We saw a median overall survival of a little over 18 months. For those who achieved what we call a ‘true (complete response)', that means that they not only clear all their leukemia cells, but they recovered their (blood) counts, too, we don’t even have an estimate for their median survival because we haven’t reached it yet,” Shah explained. “For ALL that has multiple relapses or refractory (disease), to see this is huge.”

How CAR-T Cell Therapy Works

CAR-T cell therapy works by removing patients’ blood plasma – a process called apheresis –then engineering them to better recognize and attack cancer. Before a patient undergoes apheresis, it is important that they are not on steroids or other medications that can cause their T cells to underperform. Other conditions that might hinder the health of T cells include low white blood cell counts or high levels of inflammation, Shah explained.

Before the newly engineered T cells are re-infused, the patient’s body must be primed for the process. At this point in the process, they will have their T cells depleted so that once the new blood enters their system, the body will work to reproduce it and create as many new aggressive T cells as possible.

“That’s the scenario which we want to put our CAR-T cells into, because they’re going to see this fuel and they’re going to be able to grow and functionally kill leukemia if there is sufficient fuel around them for them to do that,” Shah said. “When we say fuel…we’re talking about what are called cytokines. These are inflammatory chemicals that our body normally produces to support a whole variety of different immune functions.”

Side Effects of Tecartus

However, with the release of cytokines into the blood can come serious side effects – namely neurotoxicity and a condition called cytokine release syndrome, which could be life-threatening.

However, a safety analysis of Tecartus showed that 94% of cytokine release events and 88% of neurologic events were resolved.

“Roughly half of all ALL cases actually occur in adults, and unlike pediatric ALL, adult ALL has historically had a poor prognosis,” said Lee Greenberger, Chief Scientific Officer of The Leukemia & Lymphoma Society (LLS), in a statement. “Developing new therapies that would be life-changing for people with cancer has been a dream of LLS. We are proud to see the potential of CAR T realized for even more people with this approval for brexucabtagene autoleucel.”