– Largest Real-World Evidence (RWE) Analysis of Yescarta in Second-Line Shows 71% Overall Survival Rate, Consistent with Pivotal ZUMA-7 Study, in Broader Patient Population with Relapsed/Refractory Large B-cell Lymphoma (R/R LBCL) –
– RWE Shows Decreasing Trend Over Time of Cytokine Release Syndrome and Related Adverse Events After Yescarta Treatment in Third-Line Plus Setting –
– Findings from ALYCANTE Study Show Stable Long-Term Quality of Life for R/R LBCL Patients Treated with Yescarta –
December 08, 2024--SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announced findings from three new analyses for Yescarta ® (axicabtagene ciloleucel) that demonstrate improved outcomes for people living with relapsed or refractory (R/R) large B-cell lymphoma (LBCL), which were presented at 66 th American Society of Hematology (ASH) Annual Meeting & Exposition.
The data include findings from the largest real-world analysis of patients who received Yescarta as second-line treatment for R/R LBCL during 2022-2023 based on Center for International Blood and Marrow Transplant Research (CIBMTR) registry data (abstract #526). This real-world evidence (RWE) demonstrates high rates of overall survival (OS), overall response rate (ORR), complete response (CR), and other effectiveness measures, consistent with ZUMA-7 outcomes. Further RWE from CIBMTR demonstrate a decreasing trend in incidence, severity and duration of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS) in the third-line-plus setting during 2017-2023 (abstract #527). In addition, findings from the Phase 2 ALYCANTE study on health-related quality of life (HRQoL) outcomes following Yescarta treatment (abstract #4505), co-sponsored by the French collaborative group The Lymphoma Study Association/Lymphoma Academic Research Organization (LYSA/LYSARC) and Kite, show either stability or improvement of HRQoL three months following infusion.
“We are pleased that Yescarta’s overall survival benefit for patients with early relapsed/refractory large B-cell lymphoma is confirmed in the largest real-world analysis of a broader patient population,” said Dominique Tonelli, VP, Global Head of Medical Affairs, Kite. “By studying outcomes in the real world, we consistently demonstrate that patients treated with Yescarta have the opportunity to live longer.”
Detailed Information on Yescarta Abstracts:
Abstract #526
Real-World Early Outcomes of Second-Line Axicabtagene Ciloleucel (Axi-Cel) Therapy in Patients (Pts) With Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
The largest real-world analysis of 446 patients from 89 U.S. centers from the CIBMTR Registry with LBCL (diffuse LBCL [DLBCL], 78%; primary mediastinal LBCL [PMBCL], 3%; high-grade B-cell lymphoma, 18%; follicular lymphoma grade IIIB, 1%) who received second-line Yescarta treatment demonstrated outcomes consistent with the ZUMA-7 study across broader patient and disease characteristics than those included in the ZUMA-7 pivotal study or Phase 2 ALYCANTE study, at a median of 12-months of follow-up.
Among all patients, ORR was 79% (95% confidence interval [CI], 75–82), with a CR rate of 64% (95% CI, 60–69). The 12-month rate of duration of response (DOR) was 66% (95% CI, 59–71), progression-free survival (PFS) was 53% (48–58), event-free survival (EFS) was 53% (48–58), and OS was 71% (66–76). Any-grade CRS and ICANS were reported in 87% (Grade ≥ 3, 5%) and 50% (Grade ≥ 3, 22%), respectively.
When assessed by ZUMA-7 eligibility, ORRs in ineligible patients (n=219) versus eligible or unknown patients (n=214) were both 79%, respectively, with CR rates of 63% and 65%, respectively. At 12-months, DOR in ZUMA-7 ineligible and eligible or unknown patients were 60% and 69%, PFS were 48% and 58%, EFS were 48% and 58%, and OS were 62% and 80%, respectively. Incidence of ICANS was 54% in ZUMA-7 ineligible patients and 45% in ZUMA-7 eligible or unknown patients. Among 13 patients with PMBCL, ORR was 69% (95% CI, 39–91), all with CR. The six-month rate (95% CI) of DOR was 100%, PFS was 68%, EFS was 68%, and OS was 100%. Incidence of any-grade CRS was 85% and ICANS was 54%.
“It is reassuring that the largest real-world dataset for axi-cel as a second-line treatment for relapsed/refractory large B-cell lymphoma, across a broader patient population than the ZUMA-7 pivotal study or Phase 2 ALYCANTE study for transplant-ineligible patients, has demonstrated consistent outcomes at 12-months median follow-up as in ZUMA-7,” said Dr. Dasom (Caroline) Lee, Lead Investigator on the study and Fellow, Hematology and Medical Oncology, Stanford Medicine. “These data should provide further confidence to physicians that earlier use of axi-cel can provide the best chance for overall survival and possibly a cure for these patients.”
Abstract #527
Real-world Trends of Cytokine Release Syndrome and Neurologic Events, and Pattern of Their Management among Patients Receiving Axicabtagene Ciloleucel for Relapsed or Refractory (r/r) Large B-cell Lymphoma (LBCL) in the U.S.: a CIBMTR Report
Real-world data from 1,615 patients with R/R LBCL from 109 U.S. centers from the CIBMTR registry demonstrated a decreasing trend in incidence, severity and duration of CRS and ICANS following treatment with Yescarta for adult patients with R/R LBCL in the third-line-plus setting.
Patients who received Yescarta during 2022–2023 (n=206) and 2020–2021 (n=486) had significantly lower incidences of Grade ≥ 3 CRS compared to those treated during 2017–2019 (n=923, odds ratio [OR] 0.17, 95% CI, 0.07−0.41, and OR 0.63, 95% CI, 0.43−0.94, respectively). Furthermore, patients treated in the later time periods of 2022-2023 and 2020-2021 experienced significantly shorter duration of CRS compared to 2017-2019 (hazard ratio [HR] 1.36, 95% CI, 1.14-1.64, and HR 1.34, 95% CI, 1.18-1.52, respectively).
Patients who received Yescarta during 2022–2023 and 2020–2021 had a significantly lower incidence of any-grade ICANS compared to those treated in 2017–2019 (OR 0.47, 95% CI, 0.34−0.66, and OR 0.63, 95% CI, 0.50−0.80, respectively). The duration of ICANS was also significantly shorter for those treated in 2020-2021 compared to 2017-2019 (HR 1.21, 95% CI, 1.02-1.43)
The rates of use of tocilizumab and corticosteroids for the treatment of CRS/ICANS were consistent for the three periods, although there was an increasing trend of anakinra use (1%, 6%, and 13%, respectively). Concerning other adverse events, rates of prolonged thrombocytopenia and clinically significant infections were consistent.
“Over the past seven years, there has been wider adoption of CAR T-cell therapies as a standard treatment for patients, and the knowledge, skills, and experience needed to administer the therapies safely and effectively has grown,” said Dr. Jiasheng Wang, Assistant Professor of Medicine, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. “This real-world analysis reflects a growing understanding in clinical tools such as prophylactic and preemptive management strategies that can help manage axi-cel patients safely and effectively.”
Abstract #4505
Health-related quality of life after Axi-cel as a second-line therapy in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation: results of the ALYCANTE phase II trial
New HRQoL findings from the Phase 2 ALYCANTE study, led and sponsored by the French collaborative group LYSA/LYSARC, for use of Yescarta in patients with R/R LBCL after one prior line of therapy who were deemed ineligible for high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), demonstrated that after a short initial deterioration at one-month post-infusion, patients reported longer-term stable or improved quality of life across parameters, after up to 12 months of follow-up.
Findings from 61 patients included in the ALYCANTE study reported a lower symptomatic level, noted by lower HRQoL, at three months compared to baseline, with a clinically significant difference for pain (mean=11.9 [95% CI, 5.4-18.4] at three months vs. 25.1 [95% CI, 17.7-32.6] at baseline), emotional impact (mean=12.9 [95% CI, 8.6-17.2] vs. 23.8 [95% CI, 17.9-29.6]) and worries/fears about health and functioning (mean=22.1 [95% CI, 16.8-27.3] vs. 33.0 [95% CI, 27.2-38.8]).
At three months post Yescarta infusion, 45% of patients presented a stable global health condition and 73% stable physical functioning. In the longer-term, at 12 months post-infusion, patients reported stable states, with clinically and statistically significant improvement in 4/22 HRQoL measures. Analyses confirmed findings observed over time for global health status, physical functioning and visual analogue scale (VAS, common valuation method to provide a single-index measure of HRQoL) were consistent between both the ALYCANTE and pivotal ZUMA-7 study.
“ALYCANTE is the first study to assess axi-cel as second-line therapy in transplant-ineligible relapsed/refractory large B-cell lymphoma patients, with previous study findings confirming its efficacy in this patient population,” said Prof. Roch Houot, Head of Haematology Department, University Hospital of Rennes, France and coordinator of the ALYCANTE study. “This current study shows that, in this frail and elderly population, axi-cel not only increased the quantity of life but also improved the quality of life which was comparable to that of the transplant-eligible patients, and allowed recovery of a fatigue score close to the general French population.”
About LBCL
Globally, LBCL is the most common type of non-Hodgkin lymphoma . In the United States, more than 18,000 people are diagnosed with LBCL each year. About 30-40% of patients with LBCL will need second-line treatment, as their cancer will either relapse (return) or become refractory (not respond) to initial treatment.
About ALYCANTE study
ALYCANTE (NCT04531046) is a phase 2 study evaluating the efficacy and safety of Yescarta in patients with R/R LBCL after one prior line of therapy who were deemed ineligible for high-dose chemotherapy and ASCT, sponsored by the LYSA/LYSARC collaborative group. The primary endpoint was the complete metabolic response at three months from Yescarta infusion. The study was funded by Kite, a Gilead Company, and carried out with Yescarta manufactured by Kite.
About ZUMA-7 Study
Based on the primary efficacy endpoint results of ZUMA-7, the U.S. Food & Drug Administration approved Yescarta as initial treatment of R/R LBCL in April 2022. The EU granted approval in October 2022, followed by approvals in several other countries such as: Australia, Canada, Great Britain, Israel, Japan and Switzerland.
ZUMA-7 is a randomized, open-label, global, multicenter, Phase 3 study evaluating the safety and efficacy of Yescarta versus standard of care (SOC) for second-line therapy in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The SOC for initial treatment of R/R LBCL has been a multi-step process involving platinum-based salvage combination chemotherapy regimen, and for responders, HDT and ASCT. In the study, 359 patients in 77 centers around the world were randomized (1:1) to receive a single infusion of Yescarta or SOC second-line treatment. The primary endpoint was EFS as determined by blinded central review and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate and OS. Additional secondary endpoints included patient-reported outcomes (PROs) and safety. Per hierarchical testing of primary and key secondary endpoints and group sequential testing of OS, an interim analysis of OS occurred at the time of the primary EFS.
About Yescarta
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.
YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
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Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
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Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.
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Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on achieving cures with cell therapy. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company. Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial supply and commercial product manufacturing.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. Gilead acquired Kite in 2017.
About the LYSA/LYSARC Collaborative Group
LYSA, The Lymphoma Study Association, is a non-profit, internationally leading, academic cooperative group gathering multidisciplinary expertise in lymphoma. Its operational structure, LYSARC, The Lymphoma Academic Research Organization, has all the integrated functions and platforms dedicated to pathology, biology and imaging to conduct clinical studies and real-world registries, as well as exploratory research programs. The LYSA has more than 500 members, researchers and medical experts, with a network of about 90 clinical research centers in France, Belgium and Portugal. The LYSA's missions are to promote clinical research, to improve prevention, care, and treatment of patients and to disseminate knowledge about all types of lymphoma.