The approval was based on data from ZUMA-7, a phase 3 clinical trial.
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Axicabtagene ciloleucel (axi-cel; Yescarta) has been approved by the European Commission for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL) who are refractory to or have relapsed 12 months from the completion of first-line chemoimmunotherapy.1
The approval was based on data from ZUMA-7, a phase 3 clinical trial (NCT03391466). In the study, axi-cel led to a significant improvement in the primary end point of event-free survival (EFS) vs standard of care (SOC; HR, 0.40; 95% CI, 0.31-0.51; P < .001) at a median follow-up of 2 years. Median EFS for patients treated with axi-cel was 8.3 months (95% CI, 4.5-15.8) compared to 2.0 months (95% CI, 1.6-2.8) for patients receiving the SOC. Meanwhile, for patients treated with axi-cel, the 2-year EFS rate was 41% (95% CI, 33%-48%) while it was 16% (95% CI, 11%-22%) for patients treated with the SOC.1,2
This is the first approval of a CAR-T therapy in Europe for patients who did not achieve a response to first-line treatment.
“We are very proud to announce Kite’s fifth approved indication in Europe in our continued commitment to the research and delivery of cell therapies with curative potential to patients who might benefit around the world,” Christi Shaw, chief executive officer, Kite, said in a statement. “Today’s approval marks an important step by providing patients in Europe this option of CAR T-cell therapy earlier in their treatment journey.”
Axi-cel was previously approved by the FDA in April of last year for the treatment of adult patients with LBCL refractory to first-line chemoimmunotherapy or who relapse 12 months or less after first-line chemoimmunotherapy. The decision was also based on data from ZUMA-7.3
The ongoing, randomized, open-label, global, multicenter ZUMA-7 trial is evaluating the safety and efficacy of a single-infusion of axi-cel compared to the SOC. The SOC consists of platinum-based salvage chemotherapy and subsequent high-dose chemotherapy and autologous stem cell transplant in those who respond to salvage chemotherapy. The trial includes patients with relapsed/refractory LBCL within 12 months of first-line therapy. EFS is the study's primary end point, while key secondary end points include objective response rate, overall survival, patient-reported outcomes (PROs), and measures of safety.
Additional findings from the study showed that axi-cel led to an improvement in EFS across key patient subgroups, including elderly patients (HR, 0.28; 95% CI, 0.16-0.46), primary refractory patients (HR, 0.43; 95% CI, 0.32-0.57), those with HGBL (HR, 0.28; 95% CI, 0.14-0.59), and those with double-expressor lymphoma (HR, 0.42; 95% CI, 0.27-0.67).
“This approval marks a major shift in the treatment of LBCL when initial treatment has failed. In ZUMA-7, treatment with [axi-cel] resulted in an overall better outcome for patients than SOC, especially in terms of EFS, marking a new era for treatment earlier in the disease pathway for more patients,” John Gribben, professor of medical oncology at the Cancer Research UK Barts Centre in London, said.
The safety profile of the agent was also consistent with prior studies. Among the 170 axi-cel–treated patients evaluable for safety, grade 3 or greater cytokine release syndrome (CRS) and neurologic events occurred in 6% and 21% of patients, respectively. No grade 5 CRS or neurologic events occurred. In the SOC arm, 83% of patients had grade 3 or greater events, mostly involving cytopenias.
In the analysis of PROs (n = 165), axi-cel demonstrated statistically significant improvements in quality of life (QOL) at day 100 compared with those who received SOC (n = 131), using a prespecified analysis for three PRO-domains (EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QOL, and EQ-5D-5L visual analog scale [VAS]). There was also a trend toward faster recovery to baseline QOL with axi-cel vs SOC.
“The ZUMA-7 data has also broadened our understanding of this CAR T-cell therapy, allowing us to better manage or prevent [adverse] effects, which is important as it moves earlier in the treatment pathway and for older patients and those with medical conditions for whom the standard of care might have been difficult,” Gribben said.