IMMUNE CONTEXTURE ANALYSIS IN POLARIX SUGGESTS RESPONSE TO POLA‐R‐CHP TREATMENT REDUCES TUMOR MICROENVIRONMENT DEPENDENCY

Introduction: The lymphoma microenvironment contributes to clinical treatment outcome. Previously, we showed that enrichment in M1 macrophages was associated with improved outcome patients diffuse large B-cell (DLBCL) treated rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; Yan et al., 2020). In the POLARIX study (NCT03274492), polatuzumab vedotin combination rituximab, (Pola-R-CHP) demonstrated prolonged progression-free survival (PFS) versus R-CHOP previously untreated DLBCL (Tilly 2022). Here, investigate relationship between at baseline outcomes Pola-R-CHP or POLARIX. Methods: Global gene expression patterns of tumor biopsies from were generated by RNA-seq. Immune stromal cell content estimated using xCell QuanTIseq algorithms. Association infiltration scores PFS evaluated. Hazard ratios (HR) adjusted for International Prognostic Index score (2 vs. 3–5), age (≤60 >60 years), origin (activated B cell, germinal center unclassified, unknown). Results: Gene data 665 (Pola-R-CHP, n = 331; R-CHOP, 334). macrophage levels comparable arms. Quantity primary immune-related positive prognostic factor R-CHOP. High (above median) when quantified either (HR 0.60, 95% confidence interval [CI]: 0.41–0.88) 0.57, CI: 0.39–0.84). contrast, did not impact activity regimen 0.90, 0.58–1.38) 0.95, 0.62–1.46); benefit lymphomas low similar high (Figure). Enrichment various immune infiltrates linked poor arm; however, appeared be largely independent arm. research funded by: (NCT03274492) sponsored F. Hoffmann-La Roche Ltd Genentech, Inc. Third-party editorial assistance, under direction authors, provided Anna Nagy, BSc, Ashfield MedComms, an Inizio company, Ltd. Keywords: aggressive non-Hodgkin lymphoma, targeting Conflicts interests pertinent abstract Morschhauser Consultant advisory role: Ltd/Genentech, Inc., Gilead Sciences, Celgene, Bristol-Myers Squibb, AbbVie, Epizyme, Servier, AstraZeneca, Novartis, Genmab Honoraria: Chugai, Eisai Other remuneration: (Expert Testimony) K. Hatzi Employment leadership position: Stock ownership: G. Lenz Ltd, Janssen, Incyte, Genmab, Constellation, ADC Therapeutics, Karyopharm, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal/Sandoz, Eli Lilly Research funding: Bayer, MorphoSys Educational grants: Takeda, Hexal/Sandoz (Speaker's Bureau); A. Herrera Seattle Genetics, Merck, Inc./F. AstraZeneca/MedImmune, Karyopharm Regeneron, Tubulis GmbH, Pfizer, Adicet Bio, Caribou Biosciences, AbbVie Kite (a company), Therapeutics Squibb C. R. Flowers Spectrum Pharmaceuticals, Denovo Biopharma, BeiGene, Pharmacyclics, Foresight Diagnostics, Squibb/Celgene, Curio Science, npower Acerta Pharma, Janssen Oncology, TG Millennium, Alimera Xencor, 4D Adaptimmune, Amgen, Cellectis, EMD Serono, Guardant Health, Iovance Biotherapeutics, Kite/Gilead MorphoSys, Nektar, Sanofi, Ziopharm Oncology M. Trněný Novartis J. Burke Adaptive Biotechnologies, Kura, Kymera, Morphosys, Nurix, Verastem, X4 Pharmaceuticals Genetics (Speaker’s Bureau) Hou AstraZeneca P. B. Staber MSD, E. Hawkes Bristol-Meyers Antengene, Link, MSD Izutsu BeigGene, Kyowa Kirin, Ono Pharmaceutical, Mitsubishi Tanabe Eisai, Zenyaku Kogyo Kogyo, SymBio, Nihon Shinyaku, Lilly, Meiji Seika Daiichi Sankyo Yakult, Sankyo, LOXO Otsuka, Regeneron S. Le Gouill D. Belada Tucci Gentili, Sanofi Kiowa Kyrin, Incyte W. Harris Hirata Lee Y. Jiang Jardin