Glofitamab (Glofit) Plus R-CHOP Has a Favorable Safety Profile and Induces High Response Rates in Patients with Previously Untreated (1L) Large B-Cell Lymphoma (LBCL) Defined As High Risk By Circulating Tumor DNA (ctDNA) Dynamics: Preliminary Safety and Efficacy Results

Background: Up to one-third of patients (pts) with 1L LBCL treated with R-CHOP do not achieve long-term remission or cure depending on disease stage. Outcome prediction beyond the International Prognostic Index (IPI) score is difficult due to the lack of reproducibility of common biomarkers. ctDNA offers potential as a sensitive biomarker to identify newly diagnosed pts with suboptimal chemoimmunotherapy responses. Reduction of ctDNA levels after 1-2 therapy cycles in pts with 1L diffuse LBCL (DLBCL) is associated with improved survival (Kurtz et al. J Clin Oncol 2018). Whether early intervention can improve outcomes of pts with elevated on-treatment ctDNA levels is unknown. Glofitamab, a CD20xCD3 bispecific antibody, engages and redirects T cells to eliminate B cells and has received FDA and EMA approval as monotherapy for relapsed/refractory DLBCL after ≥2 prior lines of therapy. Glofit + R-CHOP has favorable safety and efficacy in 1L DLBCL (Topp et al. ASH 2022). We report initial safety and efficacy from a Phase II open-label prospective trial (NCT04980222) evaluating glofit + R-CHOP in pts with 1L LBCL defined as high risk by ctDNA dynamics. Methods: Eligible pts had 1L CD20+ LBCL, Eastern Cooperative Oncology Group performance status 0-2, and IPI 0-5 (IPI 0 for pts with bulky disease; IPI 2-5 for USA pts). During ctDNA screening, pts received R-CHOP on Day (D)1 of Cycle (C)1 and C2 (21-day cycles). In pts defined as high risk by ctDNA (