B-CELL LYMPHOMA: Durable Remission Following “Off-the-Shelf” Chimeric Antigen Receptor (CAR) T-Cells in Patients with Relapse/Refractory (R/R) B-Cell Malignancies

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March 16, 2020

SCIENTIFIC

A small phase 1 study presented in abstract form indicates feasibility and efficacy for off-the-shelf CAR-T cell therapy in CD19+ lymphoid malignancies. A generic product could significantly reduce the cost of this approach.

Durable Remission Following “Off-the-Shelf” Chimeric Antigen Receptor (CAR) T-Cells in Patients with Relapse/Refractory (R/R) B-Cell Malignancies

Introduction

CAR T-cells provide benefit in patients (pts) with R/R hematologic malignancies. Limitations including: cost, production complexity, and life-threatening toxicity impede this therapy. An “off-the-shelf” CAR product could overcome these limitations. Objectives/Methods We developed an “off-the-shelf” CD19-specific CAR T-cell by transducing the 19-28z CAR into donor EBV-specific cytotoxic lymphocytes (19-28z CAR EBV-CTL). Pts with R/R B-cell malignancies were stratified into two treatment cohorts: cohort 1 (relapse after allo/auto HSCT) or cohort 2 (CAR-EBV-CTLs as consolidative therapy after auto-HSCT; NCT 01430390).

Objectives: determine dose limiting toxicity (primary endpoint), optimal dose for multiple infusions, and disease response (dz evaluation: 1 month (B-ALL/CLL) or 3 months (NHL)).

Conclusions

We have successfully treated ten pts with encouraging preliminary results: CR in 70% (7/10) of treated pts including 100% (4/4) in NHL and 83% in recipients of 3rd party products. The absence of CRS and ICANS (neurotoxicity) is a salient feature of this therapy and this trial demonstrates that a readily accessible source of “off-the-shelf” CAR T cell product can be made available for pts without alternative therapy.

https://tct.confex.com/tct/2020/meetingapp.cgi/Paper/14627