Kite, a Gilead Company, has presented compelling new evidence supporting the use of Yescarta (axicabtagene ciloleucel) in earlier lines of treatment for relapsed/refractory large B-cell lymphoma (LBCL), with data showing superior manufacturing outcomes and enhanced T-cell characteristics when administered as second-line versus third-line therapy.
Manufacturing Advantages in Earlier Treatment Lines
The comprehensive analysis of 4,175 patients revealed statistically significant differences in manufacturing success between treatment lines. Patients receiving Yescarta as second-line treatment achieved a first-pass manufacturing success rate (FP-MSR) of 95.08% among 1,341 patients, compared to 92.48% among 2,834 patients treated in third-line and beyond settings.
This 2.60% difference translates to 26 additional successful manufacturing lots per 1,000 patients when Yescarta is used in second-line treatment. The FP-MSR, defined as the ability to manufacture and disposition patient lots within specification at first attempt, is critical for maintaining timely and dependable manufacturing processes.
"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," according to the study findings presented at the 2024 European Hematology Association Annual Congress.
Enhanced T-Cell Characteristics in Second-Line Setting
Beyond manufacturing advantages, the analysis revealed significant differences in T-cell quality between treatment lines. Evaluating patients from the ZUMA-1 (third-line) and ZUMA-7 (second-line) studies, researchers found the median percentage of naïve-like T-cells in patient leukapheresis was 9.28% (range, 0.20-45.07; n=126; P<.0001) for second-line treatment, versus 4.11% (range, 0.09-56.60; n=100) for third-line plus treatment.
This finding demonstrates that patients treated in the second-line setting displayed approximately two times as many naïve-like T-cells compared to third-line plus patients. The presence of greater naïve-like T-cell populations in initial leukapheresis material with earlier CAR T-cell therapy intervention is numerically associated with improved response rates.
Dr. Jason Westin, study lead and Director of Lymphoma Clinical Research Program at The University of Texas MD Anderson Cancer Center, emphasized the clinical significance: "Patients treated in second-line have both a higher rate of success of having their cell therapy manufactured at the first attempt, as well as twice as many, naïve-like T-cells collected during leukapheresis, both of which support patients potentially having a shorter vein-to-vein time."
Outpatient Administration Feasibility
The company also presented preliminary data supporting outpatient administration of CAR T-cell therapies. The ongoing ZUMA-24 study, a single-arm, open-label, multicenter Phase 2 trial, evaluated 30 patients who received outpatient dosing of Yescarta with prophylactic corticosteroid use. After a median follow-up of five months, the safety and efficacy profile remained consistent with previous clinical and real-world studies.
A separate real-world study from Mayo Clinic assessed outpatient administration trends for both Yescarta and Tecartus (brexucabtagene autoleucel) in patients with relapsed/refractory non-Hodgkin lymphoma. The analysis of safety endpoints, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hospitalization rates, demonstrated that outpatient administration was possible without added toxicity.
Clinical Context and Implications
Ibrahim Elhoussieny, Vice President of Medical Affairs at Kite, stated: "These new data support the potential benefit of utilizing Yescarta in earlier lines of treatment, both in terms of manufacturing success and product characteristics. Additional data support the safety and feasibility of administering CAR T-cell therapy in the outpatient setting."
The findings build upon existing evidence regarding the association between timely infusion and patient outcomes, potentially supporting more efficient utilization and delivery of CAR T-cell therapy. The manufacturing and T-cell quality advantages observed in second-line treatment could contribute to improved patient outcomes through reduced treatment delays and enhanced therapeutic material quality.
These developments come as large B-cell lymphoma remains the most common type of non-Hodgkin lymphoma globally, representing approximately 30% of all cases. While first-line treatment can be effective in around 60% of cases, up to half of these patients will experience relapse, highlighting the critical need for effective second-line treatment options.
