medwireNews: A 7-day vein-to-vein time and manageable safety profile with the chimeric antigen receptor (CAR) T-cell therapy GLPF5101 may help improve treatment attrition rates in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL), say ATALANTA-1 investigators.
The study shows that the fresh, stem-like, early memory phenotype anti-CD19 CAR-T cell therapy has “low rates of high-grade toxicities,” namely cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with R/R NHL, said the study presenter Pim Mutsaers (Erasmus MC Cancer Institute, Rotterdam, The Netherlands) at the EHA2025 Congress in Milan, Italy.
The therapy has a 4-1BB costimulatory domain and is manufactured using a decentralized platform with a 7-day vein-to-vein time, comprising leukapheresis on day 7, followed by standard conditioning chemotherapy (fludarabine and cyclophosphamide) on days 6 to 4 and then a 3-day washout period before a single infusion of GLPG5101. The first response assessment was done 28 days later.
“Short vein-to-vein time and improved safety profile of the CAR-T cell therapy may reduce overall attrition rates including patient dropouts, enable broader use of CAR-T cell therapy, and improve outcomes,” Mutsaers commented.
Indeed, in the ongoing phase 1/2 study, 64 patients underwent leukapheresis, and only 4.7% dropped out prior to infusion – two due to progressive disease and one who had an insufficient dose generated.
The presenter pointed out that “overall attrition rates including patient dropouts post leukapheresis have been reported to be as high as 33% in clinical trials and equally high in real world clinical settings, with many patients not receiving their planned CAR-T cell treatment.”
Among the 61 R/R patients who received a GLPG5101 infusion in the current study, 17 had diffuse large B-cell lymphoma (DLBCL), 12 had mantle cell lymphoma (MCL), 27 had follicular lymphoma (FL), and five had marginal zone lymphoma (MZL). The median age of the patients was 67 years and 62% were men. The participants had received a median of three prior systemic therapies and just over half (53%) were considered high risk based on their International Prognostic Index score.
The vast majority (95%) of patients received a fresh product, and most (93%) of these, or 89% overall, had a vein-to-vein time of 7 days. Mutsaers reported that “none of the patients who received a fresh product required chemotherapy bridging therapy.” Of the four patients who received GLPG5101 outside of the 7-day timeframe – including three patients who received cryopreserved product – two received it at day 8, one at day 14, and one at 21 days.
At data cutoff, efficacy data for the first 42 evaluable patients, showed “high” overall response (OR) and complete response (CR) rates, said the presenter. For DLBCL patients, these rates were a respective 69% and 54%, and for the FL and MZL patients combined they were both 95%, and both 100% for patients with MCL.
Discussing the treatment-emergent adverse events (TEAEs), Mutsaers said that “GLPG5101 demonstrates a manageable safety profile,” with serious and grade 3 or worse TEAE rates of 26% and 85% in the 14 weeks post-infusion. The most common TEAEs of any grade were neutropenia (77%), CRS (43%), leukopenia (39%), pyrexia (39%), anemia (33%), lymphopenia (26%), thrombocytopenia (25%), and ICANS (20%). Dose-limiting toxicities were reported for 8% of patients.
The presenter highlighted to delegates that there was only one case each of grade 3 or worse CRS and ICANS. The median time to onset was 7.0 and 11.5 days, respectively, with corresponding durations of 3.0 and 2.0 days.
TEAEs of grade 3 severity or worse were most often hematologic in nature, and among patients with available data, prolonged cytopenias were seen in 32.8% at 30 days after infusion and in 24.0% at 90 days. Grade 3 or worse hemophagocytic lymphohistiocytosis occurred in 3.3% of patients and infections in 4.9%.
There were six deaths in all: two due to progressive disease and four due to AEs. Deaths due to AEs included one intra-abdominal hemorrhage and one instance of pneumonia and respiratory distress considered unrelated to treatment, and one case each of COVID pneumonia and Escherichia coli sepsis considered possibly related to treatment.
The presenter highlighted that robust CAR-T cell expansion and durable persistence of up to 21 months after infusion was seen across all the tumor types, irrespective of dose. Of note, CAR-T cell expansion and persistence were higher in patients with than without CRS, whereas there was no difference between those with and without ICANS.
Concluding, Mutsaers said that “the low drop-out rates observed in ATALANTA-1, with rapid manufacturing and the 7-day vein-to-vein delivery time, potentially facilitated treatment of patients who would otherwise not be able to receive [CAR-T cell] treatment.”
He added that these benefits, together with GLPG5101’s “favorable” safety profile, suggest “the potential for future use in an outpatient setting.”
