Impact of CAR T-cell product viability on B-cell lymphoid malignancy outcomes.

CTL019 (tisagenlecleucel) is an anti-CD19 genetically modified autologous T-cell therapy approved for treatment of relapsed/refractory pediatric and young adult B-cell acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL). For CTL019 manufactured at Penn, the product release criteria include a viability assessment. In clinical trials, viability specification for product release was ≥ 70% viable cells; whereas, for commercial tisagenlecleucel, viability specification for product release was ≥ 80%. We examined the relationship between CTL019 viability release testing and clinical outcomes. We analyzed CTL019 viability release testing in patients (pts) treated on prospective single institution clinical trials for non-Hodgkin lymphomas (NHL) (NCT02030834) and pediatric ALL clinical trials (NCT01626495, NCT02906371). The relationship of CTL019 product viability release testing and overall response, progression-free survival, overall survival, sensitivity/specificity of viability testing to predict complete response, and CAR T-cell expansion were examined. For 39 NHL pts, the median product viability was 89.8% (range: 73.7%-97.7%) and 3 pts had products with < 80% viability. For 123 ALL pts, median product viability was 89.3% (range: 56.0%-98.4%); 15 pts had products with < 80% viability. For NHL pts, there was no difference in % viability for pts who had CR vs those with PR/PD (p=0.7). For ALL pts, there was no difference in viability for pts who had CR/CRi vs those with PD/NR (p=0.9). Receiver operating characteristic (ROC) area under the curve (AUC) for NHL viability was 0.47 (95%CI: 0.28-0.65) and ROC AUC for ALL viability was 0.52 (95%CI: 0.32-0.71). PFS and OS were not significantly influenced by viability release test results for NHL (PFS HR 1.0; OS not yet available) or ALL (PFS HR 1.04; OS HR 1.03). There was no difference in PFS or OS between the lowest quintile of viability and other quintiles for NHL (PFS p=0.2, OS p=0.1) or ALL (PFS p=0.1, OS p=0.1). Peak CAR T-cell expansion was not significantly correlated with viability release test results in NHL (rho=0.12, p=0.5 or ALL (rho=-0.1, p=0.45). There was no difference in peak CAR T-cell expansion between the lowest quintile of viabilities vs the other quintiles in NHL (p=0.5) or ALL (p=0.4). These results suggest that there is no dose-response relationship between CTL019 product viability (70-98%) and clinical outcomes. [ABSTRACT FROM AUTHOR]