A new study has found that GLPG5101 led to deep and durable responses in patients with high-risk, aggressive, relapsed or refractory mantle cell lymphoma (MCL). The treatment was also well tolerated.
“MCL remains incurable, and patients with relapsed/refractory disease following Bruton tyrosine kinase inhibitor (BTKi) therapy face a poor prognosis and have a high unmet medical need,” wrote the authors, led by Marie José Kersten of Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, in the Netherlands. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an effective treatment option for this patient population but “their use is limited by restricted accessibility, prolonged vein-to-vein (VTV) times, considerable attrition rates, high rates of CRS and ICANS, and suboptimal durability of responses.”
GLPG5101 is an investigational, second-generation anti-CD19 CAR T-cell therapy that has a rapid manufacturing time on a decentralized platform—and therefore a fast VTV time. Previous results from the phase 1/2 ATALANTA-1 study have shown effectiveness and manageable safety in patients with relapsed or refractory non‑Hodgkin lymphoma.
The current analysis involved a cohort of 20 patients with MCL who had a median age of 67 years and a median two prior therapies. All patients had received a BTKi, but 85% experienced relapsed or refractory disease. Most patients (70%) had high-risk MCL according to International Prognostic Index scores, and the rest had intermediate risk.
At data cutoff in April 2025, 20 patients had received leukapheresis; of those, one discontinued treatment due to disease progression, 18 received a treatment infusion, and one was awaiting infusion.
At a median follow-up of 8.7 months:
- 17 of 18 patients (94%) received a fresh product with VTT of seven days.
- All 18 patients who received an infusion experienced a complete response.
- Eight of nine evaluable patients (89%) were negative for minimal residual disease at the time of complete response.
- None of the patients had required bridging chemotherapy.
The study also found a manageable safety profile. The most common grade 3 or higher adverse events were hematologic. Serious infections occurred in three patients, including one death due to E. coli sepsis six months after treatment.
Eleven patients experienced grade 1 or 2 cytokine release syndrome (65%), and five patients experienced grade 1 immune effector cell-associated neurotoxicity syndrome (29%). Grade 3 or higher cytopenia occurred in five patients (29%) 30 days after infusion, four patients (24%) 60 days after infusion, and four patients (27%) 90 days after infusion.
The authors concluded that the results support further development and study of GLPG5101 for relapsed and refractory MCL.
Reference
Kersten MJ, Vermaat J, Mutsaers P, et al. High complete response rates and minimal residual disease (MRD) negativity, with durable responses, in high-risk mantle cell lymphoma (MCL) with GLPG5101, a fresh, early memory-enriched CAR T-cell therapy with a 7-day vein-to-vein time: Results from the ATALANTA-1 MCL cohort. Abstract abs25-11098. Presented at: the 67th American Society of Hematology Annual Meeting and Exposition, Dec. 6-9, 2025, Orlando, FL.
