European Commission Approves Second-line Axi-cel for DLBCL/HGBL

The European Commission has approved axicabtagene ciloleucel (axi-cel; Yescarta) for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL) who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy.¹

The approval is based on findings from the pivotal phase 3 ZUMA-7 trial (NCT03391466), where at a median follow-up of 2 years, 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). The median EFS was 8.3 months (95% CI, 4.5-15.8) vs 2.0 months (95% CI, 1.6-2.8) with axi-cel and SOC, respectively. The 2-year EFS rate was 41% (95% CI, 33%-48%) with axi-cel vs 16% (95% CI, 11%-22%) with SOC.^1,2

Axi-cel is now the first CAR T-cell therapy approved for patients in Europe who do not respond 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 of Kite, said in a press release. “Today’s approval marks an important step by providing patients in Europe this option of CAR T-cell therapy earlier in their treatment journey.”

In April 2022, axi-cel received approval from the FDA for the treatment of adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy, based on findings from the ZUMA-7 trial.³

ZUMA-7 is an ongoing, randomized, open-label, global, multicenter phase 3 study evaluating the safety and efficacy of a single-infusion of axi-cel vs SOC, consisting of platinum-based salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant in those who respond to salvage chemotherapy, in patients with relapsed/refractory LBCL within 12 months of first-line therapy.

The primary end point is EFS. Key secondary end points include objective response rate, overall survival, patient-reported outcomes (PROs), and 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.

References

1. Kite’s Yescarta first CAR T-cell therapy to receive European marketing authorization for use in second-line diffuse large B-cell lymphoma and high-grade B-cell lymphoma. News release. Kite. October 17, 2022. Accessed October 18, 2022. https://bit.ly/3EMTI1O
2. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133
3. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. Accessed October 18, 2022. https://bit.ly/3iSQ8XT