Overall, approximately 41% of those receiving Axi-cel and 16% of those receiving standard of care survived for 2 years without needing additional cancer treatment or experiencing cancer progression.
Data from the 2-year ZUMA trial primary analysis show that the chimerica antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (Axi-cel) significantly improved event-free survival (EFS) compared to standard of care for patients with aggressive large B-cell lymphoma (LBCL) meeting the trial's primary endpoint, according to a study presented at the American Society of Hematology 2021 conference.
Patients who received Axi-cel survived without needing additional cancer treatment or experiencing cancer progression for a median of 8.3 months, whereas those receiving standard of care had a median EFS of 2 months. Overall, approximately 41% of those receiving Axi-cel and 16% of those receiving standard of care survived for 2 years without needing additional cancer treatment or experiencing cancer progression.
Axi-cel is currently approved by the FDA as a third-line therapy for LBCL, and 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, in the press release. “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 LBCL who had previously undergone front-line chemotherapy and were intended to proceed to stem cell transplantation. The data for overall survival are not yet established. Patients administered Axi-cel had a higher rate of EFS 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, according to the study.
Rates of adverse events (AEs) were similar between both study arms, with grade 3 or higher AEs occurring in 91% of patients receiving Axi-cel and 83% of those receiving standard of care. The most common AE in both groups was cytopenia, with previous studies finding this kind of therapy leading to cytokine release syndrome (CRS) and neurologic events.
In this specific trial, 6% of patients receiving Axi-cel experienced CRS of grade 3 or higher, 21% experienced neurologic events of grade 3 or higher, and 12% experienced changes in brain function which were temporary in most cases. Among the patients who received standard of care, 27% had a 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,” Locke said in the press release. “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.”
A limitation of the trial was that it did not include crossover between study arms, but did allow progressing patients to receive any subsequent anti-cancer treatment, including CAR T-cell therapy, as a standard of care for third line or later treatment. The researchers will be continuing to follow these patients to analyze outcomes among subgroups.
Researchers examine opportunities for immune-modulating approaches to improve outcomes and reduce side effects- ZUMA-7 demonstrates lasting benefits of car-t therapy over current standard of care for large b-cell lymphoma. December 11, 2021. Accessed December 13, 2021. https://www.hematology.org/newsroom/press-releases/2021/new-studies-highlight-how-immunotherapies-are-transforming-care-for-blood-cancers