Glofitamab-Based Therapy for Relapsed or Refractory CNS Lymphoma: A Multicenter Retrospective Study

Abstract Relapsed or refractory central nervous system lymphoma (R/R CNSL) has limited treatment options. This multicenter retrospective study enrolled 84 consecutive patients with R/R CNSL [median age, 59 years; median of 2.5 prior lines of therapy; 53 primary CNSL (PCNSL) and 31 secondary CNSL (SCNSL)] to evaluate the efficacy and safety profiles of glofitamab therapy. For PCNSL, the objective response rate (ORR) was 88% and complete response rate (CRR) was 59% with glofitamab monotherapy (n = 32) and 100% and 81% with combination therapy (n = 21), respectively. For SCNSL, ORR and CRR were 88% and 75% with glofitamab monotherapy (n = 8) and 91% and 65% with combination therapy (n = 23). At 14.7 months of follow-up, median progression-free survival was 19.5 months for PCNSL and 13.5 months for SCNSL. Cytokine release syndrome occurred in 40% (all grades 1–2) of patients, and immune effector cell–associated neurotoxicity syndrome occurred in 8%. Glofitamab-based therapy demonstrated substantial activity with manageable toxicity in this study, offering a promising treatment paradigm for patients with R/R CNSL. Significance: Effective therapies are urgently needed for R/R CNSL. Glofitamab-based therapy demonstrated high response rates in PCNSL (ORR, 92%; CRR, 68%) and SCNSL (ORR, 90%; CRR, 68%) with manageable toxicity in 84 consecutive, heavily pretreated patients, establishing a promising treatment option for this high-risk population.