Kite, a Gilead Company announces that the European Commission (EC) has granted approval for the use of Yescarta (axicabtagene ciloleucel) for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy. The approval is based on results from the pivotal Phase 3 ZUMA-7 study, the largest and longest trial of a CAR T-cell therapy versus SOC in this patient population. Yescarta is now the first Chimeric Antigen Receptor (CAR) T-cell therapy approved for patients in Europe who do not respond to first-line treatment. This provides an important additional treatment option for the most common form of non-Hodgkin lymphoma. Although 60% of newly diagnosed LBCL patients, including those with DLBCL, will respond to their initial treatment, 40% will relapse or will not respond and need second-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,” said Christi Shaw, CEO, Kite. “Today’s approval marks an important step by providing patients in Europe this option of CAR T-cell therapy earlier in their treatment journey.”
SOC therapy for this patient population has historically been a multi-step process expected to end with a stem cell transplant. The process starts with chemoimmunotherapy, and if a patient responds to and can tolerate further treatment, they move on to high-dose chemotherapy (HDT) followed by a stem cell transplant (ASCT).
“This approval marks a major shift in the treatment of LBCL when initial treatment has failed. In ZUMA-7, treatment with axicabtagene ciloleucel resulted in an overall better outcome for patients than standard of care, especially in terms of event-free survival, marking a new era for treatment earlier in the disease pathway for more patients,” said Professor John Gribben, Professor of Medical Oncology at the Cancer Research UK Barts Centre, London. “The ZUMA-7 data has also broadened our understanding of this CAR T-cell therapy, allowing us to better manage or prevent side-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.”
The ZUMA-7 study demonstrated that at a median follow-up of two years, Yescarta-treated patients had a four-fold greater improvement in the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.001) over the current SOC (8.3 months vs 2.0 months). Additionally, Yescarta demonstrated a 2.5 fold increase in patients who were alive at two years without disease progression or need for additional cancer treatment vs SOC (41% v 16%). Improvements in EFS with Yescarta were consistent 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]), high-grade B-cell lymphoma (HR: 0.28 [95% CI: 0.14-0.59]), and double-expressor lymphoma patients (HR: 0.42 [95% CI: 0.27-0.67]).
In the ZUMA-7 trial, Yescarta had a safety profile that was consistent with previous studies. Among the 170 Yescarta-treated patients evaluable for safety, Grade ≥3 cytokine release syndrome (CRS) and neurologic events were observed 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 events, mostly cytopenias (low blood counts).