Sequencing Immunotherapy in Relapsed or Refractory r/r DLBCL: Where Does Glofitamab Stand in the Post–CAR-T Era?

Abstract

Relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) continues to portend dismal outcomes following successive lines of therapy, particularly in patients progressing after chimeric antigen receptor T-cell interventions, thereby necessitating the urgent integration of novel immunotherapeutic paradigms. Glofitamab, a bispecific antibody with a distinctive 2:1 configuration targeting CD20 on malignant B cells and CD3 on T cells, has demonstrated clinically meaningful efficacy in heavily pretreated populations by potentiating endogenous cytotoxic immune responses. Across pivotal and real-world studies, glofitamab has yielded substantial response rates, including durable complete remissions, even among patients previously exposed to cellular therapies, while maintaining a manageable safety profile characterized predominantly by low-grade cytokine release syndrome mitigated through step-up dosing and anti-CD20 pretreatment. Notwithstanding these advances, questions pertaining to long-term durability, optimal therapeutic sequencing, and biomarker-driven patient selection remain unresolved. Collectively, these data position glofitamab as a compelling, off-the-shelf immunotherapeutic modality with the potential to recalibrate treatment strategies in aggressive B-cell lymphomas, pending further validation in earlier lines and combinatorial settings.