Gilead Kite declares positive trial results of T-cell Therapy Yescarta in Relapsed/Refractory Large B-cell Lymphoma

The ALYCANTE study, a multicenter, open-label Phase 2 LYSA study, evaluated for the first time the efficacy and safety of Yescarta as a second-line therapy in 62 patients with R/R LBCL who were deemed ineligible for HDCT and ASCT. The study met its primary endpoint, with a complete metabolic response (CMR) of 71% (n=44, 95% confidence interval [CI], 58.1%–81.8%) at 3 months versus 12% expected with standard of care (based on historical controls). At 6 months, 59.7% of patients (n=37) remained in CMR. CMR is defined as negative findings on a PET study during or following antitumor therapy.

“Transplant ineligible patients with aggressive relapsed or refractory B-cell lymphomas face poor prognosis,” said Prof. Roch Houot, Head of Haematology Department, University Hospital of Rennes, France and coordinator of the ALYCANTE study. “ALYCANTE is the first study to assess axicabtagene ciloleucel as second-line therapy for transplant ineligible R/R LBCL and the results showed high response rates and durable remission in this hard-to-treat population.”

Best objective response (OR) and complete response (CR) rates were 91.9% (n=57) and 82.3% (n=51), respectively. After a median follow-up of 12 months, median progression-free survival (PFS) from infusion was 11.8 months, and 48.8% (95% CI, 34.0-62.0%) of patients evaluated were alive and progression-free at 12 months. Median overall survival (OS) was not reached. OS at 12 months was 78.3% (95% CI, 64.7-87.1%). Yescarta showed an acceptable safety profile in this population, who are considered unfit for HDCT/ASCT; 8.1% (n=5) and 14.5% (n=9) experienced Grade 3-4 cytokine-release syndrome (CRS) or Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS), respectively. 

In clinical practice, about half of patients with R/R LBCL are considered ineligible for HDCT/ASCT due to factors including advanced age, frailty, and coexisting medical conditions. The ALYCANTE study included patients deemed ineligible for HDCT/ASCT because of age ≥65 years (88.7%), high hematopoietic cell transplantation-specific comorbidity index score ≥3 (32.3%), and/or prior ASCT (3.2%).

“For patients who are deemed ineligible for stem cell transplant, the ALYCANTE data demonstrate that Yescarta can provide another option for a potential curative therapy,” said Frank Neumann, MD, PhD, SVP, Kite’s Global Head of Clinical Development. “The data generation for Yescarta continues to reaffirm its potential to bring hope to patients suffering from a variety of sub-types of large B-cell lymphoma and follicular lymphoma.”

Reference: Houot, R., Bachy, E., Cartron, G. et al. Axicabtagene ciloleucel in large B cell lymphoma ineligible for autologous stem cell transplantation: the phase 2 ALYCANTE trial. Nat Med (2023). https://doi.org/10.1038/s41591-023-02572-5