Kite, a Gilead Company announced results from three new analyses for Yescarta® (axicabtagene ciloleucel) in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), including both new clinical research and real-world evidence highlighting manufacturing and product characteristics of Yescarta, and outpatient administration of both Yescarta and Tecartus® (brexucabtagene autoleucel) at the 2024 European Hematology Association (EHA) Annual Congress, June 13-16, Madrid. Results include a comparative analysis of real-world and clinical trial data (abstract P1425), which show higher manufacturing success rate and improved T-cell performance for Yescarta in second-line versus third-line plus treatment of R/R LBCL. Rapid and efficient manufacturing of CAR T-cell therapy can help reduce the time from leukapheresis to cell therapy infusion.

Real-World Manufacturing Experience of Axicabtagene Ciloleucel for Patients with Relapsed or Refractory Large B-Cell Lymphoma Treated in Second Line versus Third Line of Therapy and Beyond. An analysis of 4,175 patients compared the real-world manufacturing experience and clinical trial product characteristics for patients with R/R LBCL in second-line versus third-line plus treatment. The analysis found a statistically significant higher number of patients with R/R LBCL who received Yescarta as a second-line treatment (95.08% of 1,341 patients) achieved first-pass manufacturing success rate (FP-MSR); compared with patients treated third-line and beyond (92.48% of the 2,834).

This 2.60% difference suggests that 26 more lots of Yescarta are successfully manufactured per 1,000 in the first attempt for patients in second-line versus patients in third-line or beyond. The FP-MSR is defined as the ability to manufacture and disposition patient lots within specification at first attempt, critical to maintaining a timely and dependable manufacturing process. Given that higher FP-MSR lessens the need for multiple manufacturing attempts, patients receiving Yescarta in second-line could potentially experience shorter vein-to-vein times.

Results further assessed the percentage of naïve-like T-cells in apheresis among evaluable patients from ZUMA-1 (third-line) and ZUMA-7 (second-line). The analysis found the median percentage of naïve-like T-cells in patient leukapheresis was 9.28% (range, 0.20-45.07; n=126; P<0.0001) for second-line, versus 4.11% (range, 0.09-56.60; n=100) for third-line plus; demonstrating patients treated in second-line setting displayed a median of approximately two times as many naïve-like T-cells versus third-line plus patients. These results indicate capturing a greater naïve-like T-cell population in the initial leukapheresis material with earlier CAR T-cell therapy intervention, which is numerically associated with improved response.

Kite will also present two studies which evaluate the safety and efficacy of cell therapy administration within the outpatient setting. Preliminary findings, including safety data, from the ZUMA-24 study suggest that outpatient administration of Yescarta is feasible, when administered at a qualified treatment center, at the physician?s discretion with appropriate monitoring. The REMS program for healthcare facilities that dispense and administer Yescarta.

ZUMA-24 Preliminary Analysis: A Phase 2 Study of Axicabtagene Ciloleucel in the Outpatient Setting with Prophylactic Corticosteroids in Patients with Relapsed/Refractory Large B-Cell Lymphoma. ZUMA-24 is an ongoing, single-arm, open-label, multicenter, Phase 2 study evaluating the safety and efficacy of Yescarta with prophylactic corticosteroid use in patients with R/R LBCL, after one or more prior lines of therapy, in the outpatient setting. The preliminary analysis of 30 patients who underwent outpatient dosing of Yescarta, after a median follow-up of five months, demonstrated that the safety and efficacy of Yescarta was consistent with previous clinical and real-world studies.

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. 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.

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).

CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL) receiving YESCARTA, including = Grade 3 (Lee grading system) CRS in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including = Grade 3 CRS in 9%.

Among patients with LBCL who died after receiving YESCARTA, four had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1 to 10 days) and the median duration was 7 days (range: 2 to 43 days).

CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including = Grade 3 CRS in 8%. Among patients with iNHL who died after receiving YESCARTA, one patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1 to 20 days) and the median duration was 6 days (range: 1 to 27 days) for patients with iNHL.