In patients with relapsed or refractory non-Hodgkin lymphoma (R/R NHL), a fresh, stem-like, early memory phenotype CD19-directed chimeric antigen receptor (CAR) T-cell therapy, dubbed GLPG5101, demonstrated a manageable safety profile in the ongoing phase I/II ATALANTA-1 study. The safety data on the CAR T-cell therapy, which is manufactured using a decentralized platform with a seven-day vein-to-vein time, were presented at the European Hematology Association 2025 Congress.
“The current practice is centralized manufacturing by a pharmaceutical company. This usually involves cryopreservation, shipment from and to the hospital, and QC/QP [quality control/qualified person] release, which can be time consuming,” said presenting author Pim Mutsaers, MD, an internist-hematologist and clinical immunologist at Erasmus MC Cancer Institute in Rotterdam, Netherlands. “Decentralized manufacturing allows for much quicker manufacturing since the shipment steps are not necessary. This would potentially allow for more patients to be eligible for this therapy since the vein-to-vein time is much shorter.”
The study enrolled patients with R/R NHL, including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). The pooled results included those from all patients who received an infusion at one of three dose levels: 35-50 × 106, 85-110 × 106, or 200-250 × 106 CAR+ T cells.
As of October 14, 2024, 64 patients (DLBCL = 17; MCL = 13; FL = 29; MZL = 5) underwent leukapheresis. Patients had received a median of three (range = 1-9) prior systemic lines of therapy. Three patients dropped out before infusion. Of the 61 patients receiving an infusion, 95% received a fresh product and 5% received a cryopreserved product. Patients who received a fresh product did not require bridging therapy.
During the treatment period, occurring at 14 weeks or less post-infusion, the most common treatment-emergent adverse events (TEAEs) of any grade observed in 20% or more of patients included neutropenia (77%), cytokine release syndrome (CRS; 43%), leukopenia (39%), pyrexia (39%), anemia (33%), lymphopenia (26%), thrombocytopenia (25%), and immune effector cell-associated neurotoxicity syndrome (ICANS; 20%).
“Cases of CRS and ICANS were few and predominantly low grade, with only a single grade 3 report of each,” the authors reported.
The most common grade 3 or higher TEAEs were hematologic. Grade 3 hemophagocytic lymphohistiocytosis occurred in 3% of patients and grade 3 or higher infections occurred in 5% of patients. The researchers reported prolonged grade 3 or higher cytopenias in 33% of patients 30 days after infusion and in 24% of patients 90 days after infusion. The rate of dose-limiting toxicities stood at 8%. Six patients died, with two deaths due to progressive disease and four due AEs (one from intra-abdominal hemorrhage, one from pneumonia and respiratory distress considered unrelated to infusion, one from COVID-19 pneumonia, and one from E. coli sepsis during the follow-up period, considered possibly related to infusion).
Additionally, the results showed a robust CAR T-cell expansion and durable persistence of up to 21 months after infusion in all tumor types and phases and at all doses.
“The take-away message is that decentralized manufacturing is safe and feasible and allows for shorter vein-to-vein times,” Dr. Mutsaers concluded.
Conflicts of interest from the authors were not published in the original abstract.
Reference
Vermaat J, Anguille S, Kuipers M, et al. Low rates of high-grade toxicities with GLPG5101, a fresh, stem-like, early memory phenotype anti-CD19 CAR T-cell therapy in patients with non-Hodgkin lymphoma in the Atalanta-1 study. Abstract S281. Presented at the European Hematology Association (EHA) 2025 Congress; June 15, 2025; Milan, Italy.
