Japan Approves Second-line Axi-cel for LBCL

Japan’s Ministry of Health, Labor and Welfare (MHLW) has approved axicabtagene ciloleucel (axi-cel; Yescarta) for the initial treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, transformed follicular lymphoma, and high-grade B-cell lymphoma (HGBL).¹

The approval was supported by data from the pivotal phase 3 ZUMA-7 trial (NCT03391466), which showed that at a median follow-up of 2 years, axi-cel induced a significant improvement in 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) in the axi-cel arm vs 2.0 months (95% CI, 1.6-2.8) in the SOC arm. The 2-year EFS rate was 41% (95% CI, 33%-48%) with axi-cel vs 16% (95% CI, 11%-22%) with SOC.^1,2

“We are glad to have achieved this important milestone in order to provide an innovative treatment option to more patients with LBCL in Japan,” Wataru Takasaki, PhD, executive officer, head of R&D Division in Japan, Daiichi Sankyo, stated in a press release. “It also further demonstrates the expertise of our Daiichi Sankyo R&D organization as we had successfully expanded the indication for this CAR-T modality.”

In April 2022, the FDA approved axi-cel for the treatment of adult patients with LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.³ In October 2022, the European Commission approved axi-cel for the treatment of adult patients with DLBCL or HGBL who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy.⁴ Both approvals were based on findings from ZUMA-7.

The ongoing, randomized, open-label, global, multicenter ZUMA-7 study is evaluating the safety and efficacy of a single infusion of axi-cel vs SOC in patients with relapsed/refractory LBCL within 12 months of first-line therapy. Patients in the control arm were assigned platinum-based salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT) for those who respond to salvage chemotherapy.

Patients are required to be at least 18 years of age with LBCL that was relapsed or refractory within 1 year of frontline treatment and have intention to proceed to consolidation HDT-ASCT.

Enrolled patients were randomly assigned 1:1 to receive either a single infusion of axi-cel or SOC. EFS is the primary end point. Key secondary end points include objective response rate, overall survival, patient-reported outcomes (PROs), and safety.

Additional data 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).

Investigators found that the toxicity profile of axi-cel was consistent with prior studies. Among the 170 patients in the experimental arm evaluable for safety, 6% experienced grade 3 or higher cytokine release syndrome (CRS) and 21% experienced neurologic events. There were no grade 5 CRS or neurologic events reported.

In the analysis of PROs, patients assigned to axi-cel (n = 165) enjoyed statistically significant improvements in quality of life (QOL) at day 100 compared with those given 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). There was also a trend toward faster recovery to baseline QOL with axi-cel vs SOC.

“We are very proud of this additional [axi-cel] approval in Japan,” Christi Shaw, chief executive officer of Kite, said. “As Japan has the second-largest number of people diagnosed with non-Hodgkin lymphoma globally, this approval marks an important step in bringing this innovative therapy earlier to more patients.”

References

1. Yescarta® now approved in Japan for initial treatment of relapsed/refractory large B-cell lymphoma. News release. Kite. December 22, 2022. Accessed December 23, 2022. https://bit.ly/3FQTQMt
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
4. 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