Analyses of Yescarta CAR T-cell therapy support curative potential in patients with non-Hodgkin lymphomas – Kite/Gilead Sciences

Kite, a Gilead Company announced data from follow-up analyses of three studies of Yescarta (axicabtagene ciloleucel) that demonstrate the long-term survival potential for patients living with several sub-types of relapsed or refractory (R/R) non-Hodgkin lymphoma, which were presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition.

This included ZUMA-1 (Abstract #4864) showing that patients with refractory large B-cell lymphoma (LBCL) who maintained a complete response (CR) at 12- and 24-months following treatment with Yescarta had a 72-month estimated disease-specific survival (DSS) of 94.4% and 100%, respectively. Long-term data from the ZUMA-5 (Abstract #4868) and ZUMA-7 (Abstract #1761) studies were also presented.

“As we continue to follow up with patients living with difficult-to-treat types of lymphomas, we are witnessing a pattern of longer-term survival with a one-time treatment with Yescarta,” said Frank Neumann, MD, PhD, Senior Vice President, Global Head of Clinical Development, Kite. “The results of these studies, coupled with our rapid and reliable manufacturing, add to our body of knowledge on the benefits and utility of Yescarta as a treatment with curative intent, changing the way these cancers are treated and providing hope to thousands of lymphoma patients.”

Detailed Information on Yescarta Abstracts : Abstract #4864 -“Curative Potential of Axicabtagene Ciloleucel (Axi-Cel): an Exploratory Long-Term Survival Assessment in Patients with Refractory Large B-Cell Lymphoma from ZUMA-1.”: ZUMA-1 is an ongoing, multicenter, single-arm, open-label Phase 1/II trial evaluating the safety and efficacy of Yescarta CAR T-cell therapy in adult patients with refractory LBCL. In this post hoc analysis of ZUMA-1, with up to six years of follow-up, the five-year long-term lymphoma-related event-free survival (LREFS) was used as a measure to explore Yescarta’s curative potential. Yescarta had long-term LREFS in a substantial proportion of patients, with a five-year rate of 34% (57% among patients who achieved a CR). Additionally, this exploratory analysis found that, at six years, median overall survival (OS) remained consistent with prior analyses at 25.8 months (95% Confidence Interval [CI], 12.8-63.7) and patients who had a CR at 12 and 24 months had a 72-month DSS of 94.4% and 100%, respectively, which may be predictive of extended OS. Among patients who had a CR to therapy, the leading risks of death were reasons other than progression or adverse events after month 24 post-infusion.

Abstract #4868- “Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 4-Year Follow-Up from the Phase II ZUMA-5 Trial” : ZUMA-5 is an ongoing, single-arm, open-label, international, multicenter Phase II trial evaluating 122 adult patients with R/R indolent non-Hodgkin lymphoma (iNHL; follicular lymphoma [FL] and marginal zone lymphoma [MZL]). In this study, at a median follow-up of 52.5 months (range, 20.3-69.4; FL: 53.7, MZL: 43.8), the overall response rate (ORR) remained consistent with prior analyses (90% ORR, 75% CR rate) and the median duration of response (DOR) was 55.5 months (95% CI, 38.6-not estimable [NE]; FL: 55.5, MZL: not reached). At data cutoff, four years of follow-up, median progression free survival (PFS) was 57.3 months (95% CI, 34.9-NE; FL: 57.3, MZL: 46.9) and the 48-month OS rate was 72% (FL: 72%, MZL: 68%). No new neurologic events, hypogammaglobulinemia cases, Grade greater than 3 cytopenias or Grade greater than 3 infections occurred in the four-year analysis compared to the three-year analysis.

“Taken together with other studies, the results we saw in our four-year analysis from the ZUMA-5 trial and up to six years of follow-up from the ZUMA-1 trial support the durability and safety of axi-cel in patients with follicular lymphoma and large B-cell lymphoma who have progressed following previous lines of therapy,” said Dr. Sattva S. Neelapu, The University of Texas MD Anderson Cancer Center. “We are encouraged by these data, particularly the continued durable response and long-term survival in these patient populations that speak to the potentially curative benefit of this therapy. As we continue to follow these patients, our hope is that these positive survival trends are sustained.”

Abstract #1761- “Improved Overall Survival With Axicabtagene Ciloleucel vs Standard of Care in Second-Line Large B-Cell Lymphoma Among the Elderly: A Subgroup Analysis of ZUMA-7”-: ZUMA-7 is a randomized, open-label, global, multicenter, Phase III trial evaluating the safety and efficacy of Yescarta versus standard of care (SOC; [chemoimmunotherapy followed by HDT-ASCT in patients who had a response]) for treatment of adult patients with refractory LBCL or relapse within 12 months of first-line therapy. In this analysis, investigators reported updated efficacy and safety results from the primary OS analysis among ZUMA-7 patients aged greater than 65 years and greater than 70 years. At a median follow-up of 46.6 months, OS was prolonged in the Yescarta vs. SOC arm in patients aged greater than 65 years (HR, 0.691; 95% CI, 0.401-1.190) and for those greater than 70 years (HR, 0.330; 95% CI, 0.135-0.809). PFS assessed by investigator confirmed benefit of Yescarta over SOC in patients aged greater than 65 years (HR, 0.406; 95% CI, 0.230-0.715) and in patients aged greater than 70 years (HR, 0.206; 95% CI, 0.078-0.547). No new treatment-related deaths occurred since the primary event-free survival (EFS) analysis for ZUMA-7.

“Traditionally, older patients with relapsed/refractory large B-cell lymphoma have not been able to access some treatments due to presumed concerns regarding increased toxicity related to their age and comorbidities,” said Professor Marie José Kersten, Amsterdam University Medical Centers. “However, what we’re seeing with this subgroup analysis from the landmark ZUMA-7 trial, is that the data clearly support the consideration of axi-cel also for older patients with relapsed/refractory large B-cell lymphoma. As more data become available, my hope is that patients can receive the therapies that offer them the greatest chance for response and prolonged survival, regardless of age.”

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