Intratumoral T-cell composition predicts epcoritamab-based treatment efficacy in B-cell non-Hodgkin lymphomas.

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.
Competing Interests: L.F. Has received research funding from Genmab A/S, AbbVie, Inc., F. Hoffmann-La Roche AG, Genentech Inc., Innate Pharma S.A.; has provided consulting services for Genmab A/S, AbbVie, Inc., F. Hoffmann-La Roche AG, Genentech, Inc., Evolveimmune Therapeutics, Inc., Sanofi, S.A.; has served as an advisor for AbbVie, Inc., Seagen, Inc., Ipsen Biopharmaceuticals, Inc., ADC therapeutics S.A.; and has received travel reimbursement from Genmab A/S, AbbVie, Inc. S.A.V. previously served as an advisor for Immunai, has provided consulting services for ADT Therapeutics and Koch Disruptive Technologies, and has received funding from BMS. G.S. has received financial compensation for consulting services in the last 12 months from: Abbvie, Atb Therapeutics, Beigene, BMS, Genentech/Roche, Genmab, Janssen, Innate Pharma, Incyte, Ipsen, Kite/Gilead, Merck, Modex, Molecular Partners, Novartis, Nurix, Orna Therapeutics, and Treeline. He is a shareholder of Owkin. He has received research support from Abbvie, Genentech, Genmab, Janssen, Ipsen, and Nurix, which his institution managed.