September 28, 2022 Axicabtagene Ciloleucel (Yescarta) EMA Approval for B-cell Lymphoma Patients After First-Line Treatment

September 28, 2022 Axicabtagene Ciloleucel (Yescarta) EMA Approval for B-cell Lymphoma Patients After First-Line Treatment

Yescarta Approved in Europe for B-Cell Lymphoma

On September 28, 2022, the European Commission (EC) approved the CD19 CAR-T cell therapy Yescarta (axicabtagene ciloleucel) for a new indication: the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) after one line of systemic therapy.

Just at the end of June 2022, the EC had already approved Yescarta for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after three or more lines of systemic therapy.

According to Gilead’s statement on October 17, 2022, the drug became the first CAR-T cell therapy approved in Europe for patients who did not respond to first-line treatment. Although 60% of newly diagnosed LBCL patients (including DLBCL patients) respond to initial treatment, 40% relapse or are refractory, requiring second-line therapy.

Basis for Yescarta’s Approval

Study Process

This approval was based on the results of an ongoing, randomized, open-label, global, multicenter, Phase III ZUMA-7 study, which is the largest and longest study of CAR-T cell therapy versus SOC in this patient population. It aimed to evaluate the safety and efficacy of Yescarta versus standard second-line treatment in adult patients with relapsed or refractory LBCL within 12 months after first-line therapy. The primary endpoint was event-free survival (EFS). Secondary endpoints included objective response rate (ORR) and overall survival (OS). Other secondary endpoints included patient safety.

Study Results

The study enrolled 359 patients, with a median follow-up of 24.9 months. Yescarta demonstrated statistically significant and clinically meaningful superiority. Compared to standard treatment, Yescarta prolonged the event-free survival (EFS) of LBCL patients from 2.0 months to 8.3 months, a 6.3-month improvement, with 2-year EFS rates of 40.5% and 16.3%, respectively, approximately a 1.5-fold increase, and with a favorable safety profile.

Safety Events

The safety profile of Yescarta was consistent with previous studies. Among the 170 Yescarta-treated patients evaluable for safety, 6% and 21% of patients experienced Grade ≥3 cytokine release syndrome (CRS) and neurological events, respectively, but no Grade 5 CRS or neurological events were reported.

About Yescarta

Yescarta (Axicabtagene Ciloleucel, Axi-Cel) is a CD19-directed genetically modified autologous T-cell immunotherapy, initially approved in Europe in 2018. It is currently indicated for five blood cancers: diffuse large B-cell lymphoma (DLBCL); large B-cell lymphoma (LBCL); high-grade B-cell lymphoma (HGBL); primary mediastinal large B-cell lymphoma (PMBCL); and follicular lymphoma (FL).