Findings from two pre-planned, subgroup analyses of the landmark ZUMA-7 trial of Axicabtagene ciloleucel ( Yescarta ), which led to the U.S. Food and Drug Administration’s ( FDA ) expanded approval of Yescarta as initial treatment in adults with large B-cell lymphoma ( LBCL ) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy were announced.
These results have included 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 ).
In the ZUMA-7 sub-analysis of patients aged 65 and older, the primary endpoint of event-free survival ( EFS ) has 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 less than 0.0001 ), with over eight-fold greater median EFS ( 21.5 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 versus SOC ( 88% vs 52%; odds ratio, OR=8.81; descriptive P less than 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 ).
57% of patients in the SOC arm has received subsequent cellular immunotherapy ( off protocol ).
Yescarta has also shown 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 ) has shown clinically meaningful differences in QoL at Day 100 compared to patients receiving SOC ( n=42 ) for three prespecified PRO domains ( 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 less than 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, event-free survival 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 less than 0.001 for both ) and elevated and non-elevated LDH ( HR=0.32 and 0.5, respectively; descriptive P less than 0.001 for both ).
Event-free survival 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.
Globally, large B-cell lymphoma is the most common type of non-Hodgkin lymphoma ( NHL ).
In the United States, more than 18,000 people are diagnosed with large B-cell lymphoma each year.
About 30-40% of patients with large B-cell lymphoma will need second-line treatment, as their cancer will either relapse or become refractory to initial treatment. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Annual Meeting, 2022