{"doi":"10.1002/hon.6_2880","title":"CLINICAL RESPONSES TO ODRONEXTAMAB (REGN1979): CORRELATION WITH LOSS OF CD20 EXPRESSION AS A POTENTIAL MECHANISM OF RESISTANCE AND BASELINE BIOMARKERS OF TUMOR T CELLS","abstract":"Odronextamab (REGN1979) is a fully human CD20 × CD3 bispecific antibody being evaluated in patients (pts) with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). At selected doses, odronextamab has demonstrated durable response rates in pts with R/R follicular lymphoma (FL: ∼90%), and R/R diffuse large B-cell lymphoma (DLBCL: ∼60%). Tumor biopsies from a Phase 1 study (NCT02290951) were analyzed to investigate the association of B- and T-cell biomarkers with initial clinical response and with instances of subsequent progression. Tumor biopsies were collected at baseline, on treatment, and at disease progression (PD) (N=30; DLBCL n=19; FL n=9; mantle cell lymphoma n=2), and from reference B-NHL cases (N=47 at diagnosis; N=39 R/R). B-cell markers were analyzed by semi-quantitative chromogenic CD20 immunohistochemistry (IHC) and multiplex immunofluorescence. Tumor-infiltrating immune cells were analyzed by multiplex immunofluorescence. Quantitative image analysis was performed. Single-cell sequencing and flow cytometry were performed in one patient with FL with PD 6 months post-therapy. Most baseline R/R B-NHL biopsies (29/30, 96.7%) were CD20+, whereas CD19 expression was variable. Relative baseline IHC CD20 levels did not predict odronextamab response and CD20 intensity was similar in pts with FL or DLBCL. Moreover, 2/4 pts with <100% CD20+ B cells achieved durable responses. In 9/11 cases of PD on treatment with paired biopsy samples available (DLBCL n=6; FL n=3), loss of CD20 expression was observed; mutations accounting for loss of CD20 expression were defined in three of these pts (DLBCL n=2; FL n=1). These mutations were identified after PD, where pts had received an active odronextamab dose and experienced responses before progressing at weeks 24–25. Baseline T-cell infiltration was higher in pts with FL vs DLBCL in both the reference and study populations. Pts with DLBCL also had a higher median density of T-cell infiltration in odronextamab responders vs non-responders. Single-cell analysis of a fresh lymph node sample from a case of PD, occurring after a complete response to odronextamab, revealed a near-complete loss of CD20 protein expression on B cells, while maintaining CD19 and CD20 mRNA expression. CD20 expression is almost ubiquitous in R/R B-NHL biopsy samples, whereas CD19 expression is variable. Durable odronextamab responses were observed independently of variable CD20 levels by IHC; therefore, baseline CD20 IHC expression is not supported as a pt selection biomarker. Loss of CD20 cell surface expression, caused by defined mutations leading to lack of protein expression, occurred in several cases of relapsed disease, suggesting target-dependent escape. We also observed an association between T-cell infiltration at baseline and odronextamab response in DLBCL; additional studies are ongoing. The research was funded by: Regeneron Pharmaceuticals, Inc. Conflicts of interests pertinent to the abstract Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals, Inc Employment or leadership position: Regeneron Pharmaceuticals, Inc Stock ownership: Regeneron Pharmaceuticals,","journal":"Hematological Oncology","year":2021,"id":211993,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":801943,"name":"Nathalie Fiaschi","orcid":"0000-0003-2836-2751","position":1,"is_corresponding":false},{"id":801944,"name":"Raquel P. Deering","orcid":"0000-0002-8099-2665","position":2,"is_corresponding":false},{"id":801945,"name":"Ankur Dhanik","orcid":"0000-0001-9692-6980","position":3,"is_corresponding":false},{"id":23576,"name":"Kamil J. Cygan","orcid":"0000-0003-2088-474X","position":4,"is_corresponding":false},{"id":802376,"name":"W Zhang","orcid":null,"position":5,"is_corresponding":false},{"id":801946,"name":"Se Jeong","orcid":"0000-0001-5189-8138","position":6,"is_corresponding":false},{"id":229694,"name":"Stephane Pourpe","orcid":null,"position":7,"is_corresponding":false},{"id":801947,"name":"Lauren Boucher","orcid":"0000-0003-3152-6155","position":8,"is_corresponding":false},{"id":621475,"name":"Sara Hamon","orcid":"0000-0002-2413-2302","position":9,"is_corresponding":false},{"id":233360,"name":"Max S. Topp","orcid":"0000-0002-1267-5289","position":10,"is_corresponding":false},{"id":801948,"name":"Rajat Bannerji","orcid":"0000-0002-0770-644X","position":11,"is_corresponding":false},{"id":802377,"name":"Johannes Duell","orcid":null,"position":12,"is_corresponding":false},{"id":262219,"name":"Ranjana H. Advani","orcid":"0000-0002-3219-2292","position":13,"is_corresponding":false},{"id":802378,"name":"Dina M. Flink","orcid":null,"position":14,"is_corresponding":false},{"id":802379,"name":"A. Chaudhry","orcid":null,"position":15,"is_corresponding":false},{"id":802380,"name":"Andres Sirulnik","orcid":null,"position":16,"is_corresponding":false},{"id":59440,"name":"Israel Lowy","orcid":"0000-0002-5421-2485","position":17,"is_corresponding":false},{"id":254370,"name":"Andrew Murphy","orcid":"0000-0001-7039-7777","position":18,"is_corresponding":false},{"id":617315,"name":"David M. Weinreich","orcid":null,"position":19,"is_corresponding":false},{"id":802381,"name":"G.D. Yancopoulos","orcid":null,"position":20,"is_corresponding":false},{"id":557465,"name":"Gavin Thurston","orcid":"0000-0002-4105-5919","position":21,"is_corresponding":false},{"id":106448,"name":"Srikanth Ambati","orcid":null,"position":22,"is_corresponding":false},{"id":801949,"name":"Vladimir Janković","orcid":"0000-0002-4135-8629","position":23,"is_corresponding":false},{"id":801942,"name":"Jurriaan Brouwer‐Visser","orcid":"0009-0007-3839-6791","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:52:23.670339Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}