Two-year data from the ZUMA-7 trial primary analysis show that the CAR T-cell therapy axicabtagene ciloleucel (axi-cel) significantly improved event-free survival compared to standard of care for patients with aggressive large B-cell lymphoma, meeting the trial’s primary endpoint.

With a median of over two years of follow-up, patients receiving axi-cel survived without needing additional cancer treatment or experiencing cancer progression for a median of 8.3 months while those receiving standard of care had a median event-free survival of just two months.

Overall, 41% of those receiving axi-cel and 16% of those receiving standard of care survived for two years without needing additional cancer treatment or experiencing cancer progression.

The standard of care second-line treatment for this patient group consists of additional chemotherapy; if the lymphoma responds to this additional chemotherapy, patients can then be eligible to undergo high dose chemotherapy and hematopoietic stem cell transplantation. Axi-cel is currently approved by the U.S. Food and Drug Administration (FDA) as a third-line therapy for large B-cell lymphoma; the ZUMA-7 trial assessed its use as a second-line therapy.

“The results of ZUMA-7 herald a paradigm shift in how we treat large B-cell lymphoma,” said Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa. “We found that by giving axi-cel in the second line setting, patients had longer event-free survival compared to the standard of care. This is remarkable and indicates that patients with lymphoma not responding to initial treatment or relapsing within 12 months should have the opportunity to get this therapy.”

The trial enrolled 359 patients with early relapsed or refractory large B-cell lymphoma who had previously undergone front-line chemotherapy and were intended to proceed to stem cell transplantation.

Although the data for overall survival are not yet mature, those receiving axi-cel had a higher rate of event-free survival (as described above) and a higher rate of response to treatment, which occurred in 83% of patients receiving axi-cel and 50% of patients receiving standard of care.

The rates of adverse events were relatively similar between both study arms, with adverse events of grade 3 or higher occurring in 91% of patients receiving axi-cel and 83% of those receiving standard of care.

The most common event in both groups was cytopenias, or low blood cell counts.

Previous studies have found CAR T-cell therapy leads to two types of acute toxicities, which are usually transient: CRS and neurologic events.

In this trial, 6% of patients receiving axi-cel experienced CRS of grade 3 or higher, and 21% experienced neurologic events of grade 3 or higher, with 12% experiencing changes in brain function (encephalopathy), which were temporary in most cases.

Among those receiving standard of care, 27% experienced fever when their white blood cell counts were low due to chemotherapy, which is considered a serious event.

“For both study arms, the rates and types of adverse events were consistent with expectations based on previous trials and real-world experience,” Dr. Locke noted.

“By giving CAR T-cell therapy as an earlier line of treatment, we are able to reduce the amount of chemotherapy patients are exposed to and get them quickly to a definitive therapy that can eradicate lymphoma for many years, if not forever, without a stem cell transplant,” said Dr. Locke.

The trial did not include cross-over between study arms but allowed progressing patients to receive any subsequent anti-cancer therapy including CAR T-cell therapy as a standard of care for third line or later treatment.

Ultimately, 56% of those randomized to receive standard of care received CAR T-cell therapy after their cancer progressed.

Source: ASH