The Dutch CAR-T Tumorboard Experience: Population-Based Real-World Data on Patients with Relapsed or Refractory Large B-Cell Lymphoma Referred for CD19-Directed CAR T-Cell Therapy in The Netherlands

Abstract

The real-world results of chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) substantially differ across countries. In the Netherlands, the CAR-T tumorboard facilitates a unique nationwide infrastructure for referral, eligibility assessment and data collection. The aim of this study was to evaluate real-world outcomes of axicabtagene ciloleucel (axi-cel) in the Dutch population, including the thus-far underreported effects on health-related quality of life (HR-QoL). All patients with R/R LBCL after ≥2 lines of systemic therapy referred for axi-cel treatment between May 2020–May 2022 were included (N = 250). Of the 160 apheresed patients, 145 patients received an axi-cel infusion. The main reason for ineligibility was rapidly progressive disease. The outcomes are better or at least comparable to other studies (best overall response rate: 84% (complete response: 66%); 12-month progression-free-survival rate and overall survival rate: 48% and 62%, respectively). The 12-month NRM was 5%, mainly caused by infections. Clinically meaningful improvement in several HR-QoL domains was observed from Month 9 onwards. Expert-directed patient selection can support effective and sustainable application of CAR-T treatment. Matched comparisons between cohorts will help to understand the differences in outcomes across countries and select best practices. Despite the favorable results, for a considerable proportion of patients with R/R LBCL there still is an unmet medical need.

Population-Based External Validation of the EASIX Scores to Predict CAR T-Cell-Related Toxicities

“…In this population-based cohort study, all patients with r/r LBCL after ≥2 lines of systemic therapy who received axi-cel as standard of care or in an early access program between June 2019 and May 2022 in the Netherlands were included. For patients who received axi-cel as standard of care, eligibility for CAR T-cell therapy was approved by the Dutch CAR-T tumorboard according to the criteria described previously [19]. Patients received lymphodepleting chemotherapy with cyclophosphamide (500 mg/m 2 ) and fludarabine (30 mg/m 2 ) for three consecutive days (Day-5, -4, and -3) followed by a single infusion of CAR T-cells (Day 0).…”