Inferior survival in double refractory large B-cell lymphoma eligible for third-line CD19 CAR T-cell therapy

Outcomes following CD19 chimeric antigen receptor (CAR) T-cell therapy in third-line treatment and beyond for patients with large B-cell lymphoma (LBCL) refractory to both an anthracycline during initial and platinum-based salvage therapy, referred to as double refractory (DR), are not well-described. It is also unclear if these patients may be less likely to proceed to CAR T-cell infusion. Our objectives were to assess third-line CAR T-cell survival outcomes in DR- and non-DR (NDR)-LBCL cohorts including the failure rates to proceed to cell infusion. Review of 199 patients with LBCL referred for CAR T-cell treatment at our center, demonstrates that the DR-LBCL patients (n = 68) have an inferior 12-month (overall survival [OS], 47.1% vs 66.7%, respectively;) when compared to the patients with NDR-LBCL (n = 131). This OS difference is driven by a higher failure rate to proceed to CAR T-cell infusion (32% vs 18%). For patients unable to proceed to CAR T-cell infusion median OS was 2.56 months; DR-LBCL 1.94 months vs NDR-LBCL 3.42 months. The 12-month OS (65% vs 72.3%) and 6-month progression-free survival (46.5% vs 57.2%) of patients with DR- and NDR-LBCL proceeding to CAR T-cell infusion, appears similar. Our study highlights a high-risk subgroup characterized by inferior OS with challenges in getting to CAR T-cell infusion and could benefit from different management approaches such as novel bridging or "off-the-shelf" strategies.