Kite, a Gilead Company, announced five-year follow-up results from the ZUMA-5 Phase 2 study of Yescarta (axicabtagene ciloleucel) in patients with relapsed/refractory non-Hodgkin lymphomas (NHL), including follicular lymphoma (FL) or marginal zone lymphoma (MZL). The data, presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, demonstrated durable responses and long-term survival after a median follow-up of more than five years.
Sustained Clinical Benefit
The ZUMA-5 study enrolled 159 patients (127 FL, 31 MZL, 1 DLBCL). At a median follow-up of 64.6 months, the overall response rate (ORR) was 90%, and the complete response (CR) rate was 75%. Among patients who achieved a CR, 58% remained in CR at the data cutoff. The median duration of response (DOR) was 60.4 months (95% CI, 39.7-NE), with an estimated 60-month DOR of 53.4% (95% CI, 43.9-62.0).
Dr. Sattva S. Neelapu, lead investigator from The University of Texas MD Anderson Cancer Center, noted, "These impressive results demonstrate the continued durable clinical benefit and manageable long-term safety profile of axi-cel and give us hope that it may have a curative effect on these difficult-to-treat blood cancers."
Progression-Free and Overall Survival
The median progression-free survival (PFS) was 62.2 months (95% CI, 34.9-NE). The 60-month PFS rates in patients with FL were consistent regardless of high-risk characteristics. Median time to next therapy was not reached in all patients with NHL (95% CI, 38.6-NE), with a 60-month estimated rate of 53.3% (95% CI, 45.0-60.9). At data cutoff, 55% of patients (n=87) were alive with no new anticancer therapy. The median overall survival (OS) was not reached (95% CI, NE-NE), and the 60-month OS estimate was 69.0% (95% CI, 60.8-75.8).
Safety Profile
No new Yescarta-related safety signals emerged in the five-year analysis. One patient progressed after the data cutoff of the four-year analysis, and no patients died of disease progression after the prior analysis. Among treated patients (n=152), three new events not related to Yescarta were reported after the four-year analysis, including Grade 3 metastasis, Grade 1 bladder cancer, and Grade 4 myelodysplastic syndrome. One patient died of pneumonia, unrelated to Yescarta.
Implications for NHL Treatment
Dominique Tonelli, VP, Global Head of Medical Affairs, Kite, stated, "There is growing evidence that people with follicular lymphoma and marginal zone lymphoma can experience long-term survival after one Yescarta treatment... Yescarta may offer patients the chance to live longer without need for subsequent therapy and a potential cure."
These findings suggest that Yescarta could provide a curative potential for patients with relapsed or refractory NHL, addressing a significant unmet need in this patient population. The long-term data from ZUMA-5 reinforce Yescarta's role as a valuable treatment option in the landscape of NHL therapies.
