Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

作者：Michael John Dickinson, Carmelo Carlo‐Stella, Franck Morschhauser, Emmanuel Bachy, Paolo Corradini, Gloria Iacoboni, Cyrus Khan, Tomasz Wróbel, Fritz C. Offner, Marek Trněný, Shang‐Ju Wu, Guillaume Cartron, Mark Hertzberg, Anna Sureda, David Pérez-Callejo, Linda Lundberg, James Relf, Mark R. Dixon, Emma Clark, Kathryn Humphrey, Martin Hutchings · 发表于：New England Journal of Medicine · 年份：2022 · DOI：10.1056/nejmoa2206913 · 被引用次数：753 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Cutaneous lymphoproliferative disorders research

BACKGROUND: The prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is poor. Glofitamab is a bispecific antibody that recruits T cells to tumor cells. METHODS: In the phase 2 part of a phase 1-2 study, we enrolled patients with relapsed or refractory DLBCL who had received at least two lines of therapy previously. Patients received pretreatment with obinutuzumab to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy (12 cycles total). The primary end point was complete response according to assessment by an independent review committee. Key secondary end points included duration of response, survival, and safety. RESULTS: Of the 155 patients who were enrolled, 154 received at least one dose of any study treatment (obinutuzumab or glofitamab). At a median follow-up of 12.6 months, 39% (95% confidence interval [CI], 32 to 48) of the patients had a complete response according to independent review. Results were consistent among the 52 patients who had previously received chimeric antigen receptor T-cell therapy (35% of whom had a complete response). The median time to a complete response was 42 days (95% CI, 42 to 44). The majority (78%) of complete responses were ongoing at 12 months. The 12-month progression-free survival was 37% (95% CI, 28 to 46). Discontinuation of glofitamab due to adverse events occurred in 9% of the patients. The most common adverse event was cytokine release syndrome (in 63% of the p...