Kite announces three-year follow-up data from Yescarta therapy

Kite announced three-year follow-up data from the pivotal ZUMA-5 study for Yescarta in relapsed or refractory indolent non-Hodgkin lymphoma, showing continued response in 52% of all enrolled patients, and prolonged duration of progression-free survival in the Phase 2 study, presented at the 2022 American Society of Hematology Annual Meeting & Exposition. In addition, two-year follow-up data from the ZUMA-1 safety cohort evaluating use of prophylactic corticosteroids in patients with r/r large B-cell lymphoma were also presented. ZUMA-5 is a Phase 2, multi-center, single-arm study of Yescarta in patients with iNHL including follicular lymphoma and marginal zone lymphoma. Yescarta received accelerated approval from the U.S. Food and Drug Administration for the treatment of adult patients with r/r FL after two or more lines of systemic therapy in March 2021 and was approved in the European Union for the treatment of adult patients with r/r FL after three or more lines of therapy earlier this year. Yescarta is not approved anywhere in the world for MZL. 3-Year Follow-Up Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: In the ZUMA-5 study, Yescarta demonstrated continued durable responses in all patients with a median follow-up of 40.5 months.At the time of data cut-off, the overall response rate was 90% and the CR rate was 75% among all patients. Patients with FL had an ORR of 94% and patients with MZL had an ORR of 77%. Among all patients, median duration of response was 38.6 months, median DoR was not reached in patients with a CR, and median progression-free survival was 40.2 months. Compared to findings from the study’s two-year analysis, both ORR and CR rates were similar; medians for PFS had increased in MZL and remained unchanged in FL. Since the two-year analysis, no new safety signals were observed and 10 additional patients died due to the following reasons: progression, adverse events and other causes. Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel in Patients with Relapsed/Refractory Large B-Cell Lymphoma: 2-Year Follow-Up of ZUMA-1 Cohort 6L A new analysis of the ZUMA-1 safety management cohort of patients with r/r LBCL evaluating the longer-term impact of prophylactic use of corticosteroids and earlier treatment with corticosteroids and/or tocilizumab showed that the toxicity management strategy demonstrated improved long-term safety without compromising durability of response or survival in patients treated with Yescarta. Patients in the cohort received dexamethasone 10 mg orally on the day of Yescarta infusion and each of the two following days. At the time of data cut-off, the median follow-up was 26.9 months (range, 24.0-30.1). The ORR was 95% (80% CR), which was consistent with results at the one-year analysis. Median DoR was 25.9 months (95% CI; 7.8-not estimable) and median PFS was 26.8 months (95% CI; 8.7-not estimable). No Grade greater than or equal to3 cytokine release syndrome (CRS) was observed. Grade greater than or equal to3 neurologic events increased to 18% at two years. The median time to onset of any grade CRS was five days with a median duration of four days. Two new neurologic events were observed (one Grade 2 dementia unrelated to Yescarta, one Yescarta-related leukoencephalopathy that was fatal). Median time to onset of any grade neurologic event was unchanged from the one-year analysis (6 days), and the median duration was similar (19.0 days vs 18.5 days, respectively). All patients in the cohort had treatment-emergent adverse events (TEAEs), including Grade greater than or equal to3 events. The most common Grade greater than or equal to3 TEAEs were neutropenia (80%), leukopenia (40%) and thrombocytopenia (28%).