Phase I/II Study of Adaptive Manufactured Lentiviral Anti-CD20/Anti-CD19 Chimeric Antigen Receptor T Cells for Relapsed, Refractory Mantle Cell Lymphoma.

Abstract

Purpose: Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy characterized by t(11;14) and bright CD20 expression. To improve outcomes from single targeted CD19 chimeric antigen receptor (CAR) T cells, we used dual targeted lentiviral anti-CD20/anti-CD19 (LV20.19) CAR T cells as part of a phase I/II clinical trial in relapsed, refractory (R/R) MCL (ClinicalTrials.gov identifier: NCT04186520).

Methods: Patients with MCL who had failed two lines of therapy or relapsed post-transplant were eligible. LV20.19 CAR T cells were manufactured on-site via CliniMACS Prodigy using an adaptive 8- to 12-day process to optimize the final CAR product for increased numbers of naïve and stem-cell memory (SCM) like T cells.

Results: Seventeen patients with R/R MCL received a single dose of LV20.19 CAR T cells at 2.5 × 10⁶ cells/kg (phase I = three patients; phase II = 14 patients). The best overall response rate (ORR) was 100% (complete response [CR] = 88%; partial response = 12%) and the phase II efficacy threshold for day-90 CR rate was exceeded. Two patients have relapsed as of the data cutoff and neither the median progression-free survival nor overall survival has been reached with a median follow-up of 15.8 months. Ninety-four percent (n = 16) experienced cytokine release syndrome, all grade 1-2. Eighteen percent (n = 3) had immune effector cell-associated neurotoxicity syndrome in the first 28-days, two with reversible grade 3 toxicity. Three patients had nonrelapse mortality events; all occurred in the setting of ongoing B-cell aplasia. The final LV20.19 CAR products were enriched for higher percentages of T-_SCM/T-naïve cells and most patients received CAR T cells within 8 days of apheresis.

Conclusion: In conclusion, we demonstrate that on-site adaptive manufactured LV20.19 CAR T cells are feasible, safe, and efficacious for R/R MCL with best ORR of 100%, a favorable safety profile, and few relapses to date.