Sub-analyses of ZUMA-7 trial reinforce Yescarta CAR T-cell therapy superiority over standard of care as initial treatment for patients With relapsed or refractory large B-cell lymphoma. -Kite/Gilead

These results include an analysis of clinical and patient-reported outcomes (PROs) in patients aged 65 or older, as well as an exploratory analysis of the association of pre-treatment tumor characteristics with clinical outcomes in patients with both low and high tumor burden and elevated and non-elevated lactate dehydrogenase(LDH). The data were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstracts #7548 and #7565).

“Patients with large B-cell lymphoma aged 65 and above are at higher risk of not being eligible for or able to tolerate the standard of care, which can lead to poorer outcomes and health-related quality of life,” said Jason Westin, MD, MS, FACP, ZUMA-7 Principal Investigator, Director, Lymphoma Clinical Research, and Associate Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “These data demonstrate that older patients, who are frequently considered transplant-ineligible based on age, can safely receive second-line CAR T-cell therapy with curative intent.”.

In the ZUMA-7 sub-analysis of patients aged 65 and older , the primary endpoint of event-free survival (EFS) demonstrated that Yescarta (n=51) was superior to SOC (salvage chemoimmunotherapy followed by high-dose chemotherapy and stem cell transplant in those who respond; n=58; Hazard Ratio [HR], 0.276; descriptive P<0.0001), with over eight-fold greater median efs (21.5 months vs 2.5 months) and over three-fold greater estimated 24-month efs rate (47.8% vs 15.1%). objective response rate (orr) was higher with yescarta vs. soc (88% vs 52%; odds ratio: 8.81; descriptive p><0.0001). complete response (cr) rates in the yescarta group were over double that of the soc group (75% vs 33%). overall survival (os), evaluated as a preplanned interim analysis, was prolonged in the yescarta arm compared with the soc arm (hr, 0.517). fifty-seven percent of patients in the soc arm received subsequent cellular immunotherapy (off protocol).></0.0001).></0.0001),>

Yescarta also showed meaningful improvement in quality of life (QoL) over SOC with faster recovery to pre-treatment quality of life among patients 65 years of age or older. Among those evaluable for the PRO portion of the study, Yescarta (n=46) showed clinically meaningful differences in QoL at Day 100 compared to patients receiving SOC (n=42) for three prespecified PRO domains (European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ]-C30 Global Health Status/QOL, EORTC QLQ-C30 Physical Functioning, and EQ-5D-5L visual analog scale [VAS]). For all three domains, scores continued to favor Yescarta over SOC at Day 150 (descriptive P<0.05).></0.05).>

The safety profile of Yescarta was consistent with previous studies and real-world data in patients of all ages . Rates of cytokine release syndrome (CRS) and neurologic events (NE) for patients 65 and older were slightly higher than those observed in the overall patient population. Notably, compared with SOC patients, more Yescarta patients had high-risk features at baseline, including second-line age-adjusted International Prognostic Index (IPI) 2-3 (53% vs 31%), elevated LDH (61% vs 41%), and high grade B-cell lymphoma (including double/triple-hit- lymphoma (33% vs 14%)).

In a separate exploratory analysis of pre-treatment tumor characteristics including tumor burden and LDH , EFS was superior for Yescarta compared to SOC for patients with high and low pre-treatment tumor burden (HR, 0.29 and 0.49, respectively; descriptive P<0.001 for both) and elevated and non-elevated ldh (hr, 0.32 and 0.5, respectively; descriptive p><0.001 for both). efs in yescarta patients was not significantly different for patients with high or low pre-treatment tumor burden (hr, 0.92; descriptive p="0.68)" or elevated and non-elevated ldh (hr, 1.11; descriptive p="0.61)," but was worse in patients who received soc with high pre-treatment tumor burden (hr, 1.51; descriptive p="0.02)" or elevated ldh (hr, 1.56; descriptive p="0.01)." durable responses with yescarta were greatest in tumors with prominent b-cell features, but were superior to soc regardless of these features.></0.001></0.001>

"High tumor burden and elevated LDH levels are typically associated with poorer outcomes , especially when patients have exhausted treatment options,” said Frederick L. Locke, MD, ZUMA-7 Principal Investigator and Co-Leader of the Immuno-Oncology Program at Moffitt Cancer Center, Tampa, Florida. “These are factors that clinicians take into consideration when determining eligibility for standard of care in the second-line setting as well as CAR T-cell therapy in the third-line setting. In this analysis, response rates to axi-cel in the second-line setting were consistent regardless of level of tumor burden or LDH, which reaffirms that axi-cel should be considered the new standard of care in this earlier setting.”