Point-of-Care CAR T-Cell Therapy Yields 100% ORR in R/R CLL With or Without Richter’s Transformation
The phase 1/2 Euplagia-1 trial is currently ongoing in Europe.
All patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) with or without Richter’s transformation (RT) treated with point-of-care manufactured chimeric antigen receptor (CAR) T-cell therapy GLPG5201 responded in the phase 1/2 Euplagia-1 trial being conducted in Europe.
Data from Euplagia-1 were presented at the European Hematology Association (EHA) 2023 Congress, held June 8-11, both virtually and in Frankfurt, Germany, by Nuria Martínez-Cibrián, MD, Hospital Clinic de Barcelona.
“CLL and SLL remain generally incurable despite advances in treatment, and patients with RT have a poor prognosis. CAR-t therapy has shown durable antitumor responses in a broad range of B-cell malignancies, including CLL and SLL with or without RT,” first author Martínez-Cibrián and colleagues wrote in their poster. “To enable rapid treatment of patients, a standardized, decentralized workflow for fully automated CAR-T manufacturing at the point-of-care has been developed, avoiding complex logistics or cryopreservation.”
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The trial evaluated point-of-care GLPG5201 manufactured by the Lonza Cocoon platform for a 7-day vein-to-vein time in patients with CD19+ R/R CLL after at least 2 prior lines of therapy and no prior CD9-targeted therapy. After leukapheresis and a regimen of daily oral ibrutinib, patients received infusion of either 35x106 (dose level 1 [DL1]) or 100x106 (DL2) CAR T-cells. Three patients had only CLL while 4 had CLL with RT. Patients had a median age of 66 years (range, 58-71) and a median of 3 prior therapies (range, 2-4).
Investigators found that, as of January 2023, all 7 treated patients responded, for an overall response rate of 100%. Of these, 6 patients (86%) had a complete response (CR) and 1 (17%) had a partial response (PR). All patients treated at DL2 had CRs, and the patient with a PR was 1 of 4 treated at DL1. This patient later had a CD19-negative relapse with confirmed RT. Follow-up is ongoing in the study with a current duration of response of up to 7 months.
GLPG5201 was found to have strong expansion in peripheral blood. Looking at safety, no dose-limiting toxicities have been identified and the most common serious adverse events (AE) were hematologic toxicities. No immune-effector cell-associated neurotoxicity syndrome was observed and all cases of cytokine release syndrome were below grade 3, although 1 grade 2 case required intensive care unit admission and was classified as a serious AE. The case resolved after 7 days. A third dose level cohort of 300x106 CAR T-cells is planned
“GLPG5201 is a new CAR-T therapeutic option for patients with R/R CLL with or without RT, showing limited toxicity and promising efficacy based on current results. Phase 1 of the study is ongoing to establish the recommended dose for phase 2,” Martínez-Cibrián and colleagues wrote.
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