ZUMA-12 Suggests Axi-Cel May Be Curative in First-Line, High-Risk LBCL

Patients with high-risk large B-cell lymphoma (LBCL) experienced long-term durability of response to treatment with axicabtagene ciloleucel (axi-cel) in the frontline setting, according to 3-year follow-up results from the phase 2 ZUMA-12 trial.

Results come from 40 patients with LBCL followed up for a median of 48.5 months (range, 37.1-57.8 months). The complete response (CR) rate observed with axi-cel in the response-evaluable population (n=37) was 86% (95% CI, 71%-95%), which study investigators note was higher than the CR achieved in the primary analysis.

Overall, 70% (95% CI, 53%-84%) of patients in ZUMA-12 achieved a CR by 6 months after infusion. The estimated 36-month duration of response was 81.8% (95% CI, 63.9%-91.4%). However, a study investigator revealed that rates of remission and response durability were not the most interesting finding in this study.

“This is the first study to evaluate chimeric antigen receptor T-cell therapy as first-line therapy for patients with lymphoma. The study evaluated the benefit of axi-cel therapy in the highest or high-risk patients with diffuse large B-cell lymphoma. In this very high-risk group, we observed that after 3 years of follow-up, 80% of patients remain progression free,” Sattva S. Neelapu, MD, professor, and deputy department chair of the Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, told Blood Cancers Today.

Median event-free survival (EFS), and overall survival (OS) were not reached in the longer-term analysis. The estimated EFS at 36 months was 73.0% (95% CI, 55.6%-84.4%), and the estimated OS was 81.1% (95% CI, 64.4%-90.5%). It was also estimated that at month 36, the PFS would be 75.1% (95% CI, 57.5%-86.2%).

According to ZUMA-12 investigators, the safety profile of axi-cel was consistent with that observed in other studies. All patients treated with axi-cel were assessed for safety. Among these patients, five experienced an any-grade adverse event (AE). Grade 3 or higher AEs occurred in three patients, and one patient had a grade 5 AE. Serious AEs were reported in three patients.

“Although [the] ZUMA-12 study was a single-arm phase 2 study with about 40 patients, the results were extremely promising and led to the launch of the ZUMA-23 randomized phase 3 trial where axi-cel therapy will be compared head to head with standard-of-care chemoimmunotherapy in large B-cell lymphoma patients with International Prognostic Index score of 4 or 5,” said Dr. Neelapu.

Considering that the treatment landscape for LBCL needs new frontline options, and there are few patients with high-risk LBCL who enroll in clinical trials, Dr. Neelapu explained that clinicians should be recommending the ZUMA-23 trial.

“Practitioners should strongly discuss this trial option for eligible patients, as historically, such patients have had inferior outcomes with standard-of-care chemoimmunotherapy,” he said.