Axi-cel Gains European Approval for Relapsed/Refractory Follicular Lymphoma

The European Commission has granted approval to axicabtagene ciloleucel (axi-cel; Yescarta) for the treatment of adult patients with relapsed/refractory follicular lymphoma after 3 or more prior lines of systemic therapy.¹

The approval was based off data from the pivotal phase 2 ZUMA-5 trial (NCT03105336), which investigated axi-cel in patients with relapsed/refractory follicular lymphoma who had received at least 2 prior lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent.

The 24-month analysis showed that patients who received at least 3 prior lines of therapy (n = 75), axi-cel elicited an overall response rate (ORR) of 91%, including a complete response rate of 77%. The median duration of response (DOR) was 38.6 months, and at month 24, 56% of patients remained in response.

“Follicular lymphoma that has relapsed multiple times is a difficult-to-treat disease with an especially poor prognosis as only 20% of patients are still alive at 5 years after their second relapse,” Ibrahim Yakoub-Agha, MD, PhD, head of the Hematopoietic Cell Transplantation and Cellular Therapy Unit at Lille University Hospital, stated in a press release. “Ninety-one percent of patients in the ZUMA-5 study responded to [axi-cel] after 3 or more prior lines of therapy, and more than half of these were still in response 2 years later. This sign of durable remission is critical for patients who need options that can deliver long-term benefit.”

Follicular lymphoma is the second most common form of lymphoma globally, accounting for approximately 22% of all lymphoma cases worldwide. In Europe, 27,000 new cases are diagnosed each year.

“Patients with advanced relapsed or refractory follicular lymphoma have a high need for new treatment options,” Christi Shaw, chief executive officer at Kite, stated in a press release. “This is the third approved indication for a Kite cell therapy in Europe, and we are pleased to enable more patients with different lymphomas greater access to this treatment innovation.”

Previously, in March 2021, the FDA approved axi-cel for the treatment of adult patients with relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy, which was also based off findings from ZUMA-5.²

The single-arm, open-label, multicenter trial enrolled 146 patients with either follicular lymphoma (n = 124) and marginal zone lymphoma (n = 24) who had received 2 or more prior lines of systemic therapy. Patients were required to have an ECOG performance status of 0 or 1.

Following leukapheresis and conditioning chemotherapy, patients were administered an infusion of axi-cel at 2 x 10⁶ CAR T-cells/kg.

The primary end point of the trial was ORR per central review. Secondary end points included DOR, progression-free survival (PFS), overall survival (OS), safety, and blood levels of cytokines and CAR T cells.

Updated data from ZUMA-5 presented at the 2022 Transplantation & Cellular Therapy Meetings showed that at a median follow-up of 30.9 months (range, 24.7-44.3), the ORR and CR rates for all evaluable patients with follicular lymphoma were 94% and 79%, respectively (n = 86).³

Additionally, the median PFS for patients with follicular lymphoma was 39.6 months, and the median OS was not yet reached.

Among all patients in ZUMA-5 evaluable for safety (n = 119), observations were consistent with the known safety profile of axi-cel. Instances of grade 3 or higher cytokine release syndrome (CRS) occurred in 6% of patients, and grade 3 or higher neurologic adverse effects (AEs) were reported in 16% of patients.

Notably, 99% of all instances of CRS resolved by the time of data cutoff, and 60% of neurologic AEs resolved within 3 weeks. The most common AEs of any grade were CRS (77%), infections (59%), and encephalopathy (47%).

References

1. Kite’s CAR T-cell therapy Yescarta® granted European marketing authorization for the treatment of relapsed or refractory follicular lymphoma. News release. Gilead. June 28, 2022. Accessed June 28, 2022. https://bit.ly/3y36vrQ
2. US FDA approves Yescarta for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. News release. Gilead. March 5, 2021. Accessed June 28, 2022. http://bit.ly/3kOyKnb
3. Neelapu SS, Chavez JC, Sehgal AR, et al. Long-term follow-up analysis of Zuma-5: a phase 2 study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory (R/R) indolent non-hodgkin lymphoma (iNHL). Presented at: the 2022 Transplantation & Cellular Therapy Meetings; Salt Lake City, UT; April 23-26, 2022. Abstract 75.