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New Insights into Yescarta's Benefits for LBCL Patients at ASH 2025

On December 7, Kite, a Gilead Company based in Santa Monica, California, unveiled groundbreaking data regarding Yescarta® (axi-cel) demonstrating consistent safety and effectiveness in treating patients with relapsed or refractory large B-cell lymphoma (LBCL) not eligible for standard high-dose chemotherapy and autologous stem cell transplant (ASCT). The findings were showcased at the 67th Annual Meeting of the American Society of Hematology (ASH 2025), highlighting the potential of Yescarta as a transformative treatment option for this vulnerable patient population.

This innovative analysis integrates data from the pivotal Phase III ZUMA-7 trial and the Phase II ALYCANTE trial, designed by the French cooperative group LYSA and conducted by LYSARC, focusing on patients ineligible for transplantation. The results underline how Yescarta can provide substantial benefits in terms of safety, efficacy, and improvements in quality of life for LBCL patients.

Professor Roch Houot, head of the Hematology Department at the University Hospital of Rennes and coordinator for the ALYCANTE trial, emphasized during the presentation, "Patients with LBCL who cannot undergo stem cell transplantation often have limited treatment options due to age and comorbidities, leading to poor prognoses. These results advocate for the earlier consideration of Yescarta, which allows for the possibility of one-time curative treatment, establishing CAR T-cell therapy as a new standard in second-line treatment for LBCL."

The efficacy analysis included 178 patients from the ZUMA-7 trial and 69 from the ALYCANTE trial.

Two-Year Outcomes:

• - Overall Survival (OS): The combined analysis showed a 64.9% survival rate, with the ZUMA-7 trial revealing a 62.8% rate and the ALYCANTE trial showing 70.8%. This marks a significant advancement over historical rates, which hovered around 20% for R/R LBCL patients with limited treatment options.
• - Event-Free Survival (EFS): The EFS was recorded at 45.2% in the combined analysis, with ZUMA-7 at 45.4% and ALYCANTE at 44.7%.
• - Progression-Free Survival (PFS): PFS rates were noted at 47.4% combined, with ZUMA-7 at 47.6% and ALYCANTE at 46.8%.

Three-Month Insights:

• - The combined analysis identified a Complete Metabolic Response (CMR) in 55.6% of patients. Specific rates were 51.2% for ZUMA-7 and 67.7% for ALYCANTE.
• - Overall response rates (ORR) at the one-year mark showed 46.6% for the combined analysis, 46.5% for ZUMA-7, and 46.8% for ALYCANTE.
• - Among patients responding well to treatment, 61% sustained their response for one year, with median duration of response (DOR) at 61.0% combined, 60.6% for ZUMA-7, and 62.1% for ALYCANTE.

The safety analysis across 170 patients in the ZUMA-7 trial and 62 in ALYCANTE indicated comparable safety outcomes across both trials. The incidence of treatment-emergent adverse events (TEAEs) was similar between ZUMA-7 (91.2%) and ALYCANTE (88.7%), with a combined figure of 90.5%. Significant adverse events included grade 3 or higher neurological issues encountered by 19.8% (ZUMA-7: 21.2%, ALYCANTE: 16.1%), neutropenia at 64.7% (ZUMA-7: 70.0%, ALYCANTE: 50.0%), and anemia at 27.6% (ZUMA-7: 30.0%, ALYCANTE: 21.0%).

Both trials also showed that patients experienced significant long-term quality of life improvements following initial treatment challenges. Although a temporary decline in overall health status (EORTC QLQ-C30) was noticed at day 50 post-treatment (-7.2 for ZUMA-7 and -6.3 for ALYCANTE), substantial long-term improvements were illustrated with ALYCANTE participants showing significant enhancements in overall well-being (EQ-5D-5L VAS) at 9.9 after 100 days, and ZUMA-7 patients displaying similar results after 150 days. Continuous enhancement in overall QOL was observed through the 24-month mark in both trials.

Gallia Levy, MD, PhD, Senior Vice President and Global Head of Development at Kite, noted, "This analysis provides compelling evidence of Yescarta's consistent and durable efficacy and safety profile across a broad patient population with previously limited options and dire prognoses. These robust data reinforce Yescarta's potential as curative therapy and reflect Kite’s deep commitment to transforming patient outcomes."

Understanding LBCL

Large B-cell lymphoma (LBCL) remains the most prevalent type of non-Hodgkin lymphoma globally, diagnosed in over 18,000 individuals annually in the United States alone. Approximately 30-40% of LBCL patients require second-line treatment due to relapse or resistance to initial therapy.

ALYCANTE Trial Overview

The ALYCANTE trial (NCT04531046) evaluated Yescarta's efficacy and safety in patients with R/R LBCL considered ineligible for HDC and ASCT. The primary endpoint was the proportion of patients achieving CMR at three months following Yescarta administration. This trial was funded by Kite, a Gilead Company.

The Role of LYSA and LYSARC

LYSA (Lymphoma Study Association) is a prominent, non-profit research group focused on lymphoma and CLL/WM clinical studies. With over 500 experts and approximately 90 research centers in France, Belgium, and Portugal, LYSA conducts a wide array of clinical trials ranging from early treatment assessments to the development of new therapeutic strategies. On the other hand, LYSARC (Lymphoma Academic Research Organization) serves as the largest European academic organization dedicated to lymphoma and conducts numerous clinical trials at various phases while coordinating innovative projects on an international scale.

Background on ZUMA-7

The ZUMA-7 trial supported FDA approval of Yescarta for R/R LBCL in April 2022, with additional approvals following in Europe, Australia, Canada, the UK, Israel, Japan, and Switzerland. This Phase III, randomized, open-label trial compared Yescarta's safety and efficacy in second-line treatment for adults with refractory or relapsed LBCL to standard treatment, enrolling 359 patients from 77 sites globally.

In conclusion, the recent data from ASH 2025 reinforces the vital role of Yescarta in the treatment landscape of LBCL, illuminating new possibilities for improved patient outcomes and establishing a path forward for innovative therapies in hematologic malignancies.