{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:04:37Z","timestamp":1783915477238,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>Epcoritamab is a CD3\u2009\u00d7\u2009CD20 T\u2010cell\u2013engaging bispecific antibody approved for the treatment of various types of relapsed\/refractory (R\/R) large B\u2010cell lymphoma (LBCL) and R\/R follicular lymphoma (FL), after at least two lines of systemic therapy. Here, we develop and calibrate repeated time\u2010to\u2010event models to assess the impact of optimized step\u2010up dosing (SUD) regimens and the effect of intravenous fluids and\/or corticosteroids on cytokine release syndrome (CRS) risk. The analysis used pooled data from 600 patients with aggressive non\u2010Hodgkin lymphoma (aNHL) and indolent NHL (iNHL) who received subcutaneous epcoritamab in 28\u2010day\u2009cycles in the EPCORE\u00ae NHL\u20101 and EPCORE\u00ae NHL\u20103 studies (NCT03625037, NCT04542824). In the calibrated model, prior CAR T cell therapy (125\/600 patients [20.8%]) was associated with a 69.7% reduction (95% confidence interval [CI], 38.2\u201385.2) in the maximum stimulatory effect of epcoritamab on the hazard of Grade \u22652 CRS. Intravenous fluids or dexamethasone during Cycle (C)1 were associated with a 2.89\u2010fold (95% CI, 1.57\u20135.30) increase in the half\u2010maximal effective plasma concentration of epcoritamab on stimulation (S50). Furthermore, prophylaxis with intravenous fluids and dexamethasone during C1 was associated with a 3.79\u2010fold (95% CI, 1.65\u20138.73) increase in S50. Simulations show that the use of dexamethasone further reduces Grade \u22652 CRS risk compared with prednisone in patients with aNHL\/iNHL. Moreover, a 3\u2010SUD design further reduces CRS risk in patients with iNHL. Overall, our models showed that the approved 2\u2010SUD regimen for R\/R LBCL and 3\u2010SUD regimen for R\/R FL\u2014together with intravenous fluids and dexamethasone prophylaxis\u2014are adequate to reduce Grade \u22652 CRS risk.<\/jats:p>","DOI":"10.1002\/cpt.70362","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:43:26Z","timestamp":1783421006000},"page":"542-551","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epcoritamab Step\u2010Up Dosing Regimen Selection and Optimization Using Repeated Time\u2010to\u2010Event Modeling for Cytokine Release Syndrome Risk Mitigation"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8657-9436","authenticated-orcid":false,"given":"Tommy","family":"Li","sequence":"first","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1254-3339","authenticated-orcid":false,"given":"Andrew","family":"Tredennick","sequence":"additional","affiliation":[{"name":"Metrum Research Group  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Polhamus","sequence":"additional","affiliation":[{"name":"Metrum Research Group  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Putnins","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihang","family":"Liu","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinjal","family":"Sanghavi","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"Thalhauser","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3711-8718","authenticated-orcid":false,"given":"Apurvasena","family":"Parikh","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-5989","authenticated-orcid":false,"given":"Behnam","family":"Noorani","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-2025","authenticated-orcid":false,"given":"Mohamed\u2010Eslam F.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Le Gallo","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Elliott","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Gupta","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6997-5533","authenticated-orcid":false,"given":"Steven","family":"Xu","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00889-8"},{"key":"e_1_2_11_2_1","unstructured":"Genmab [press release].TEPKINLY\u00ae (epcoritamab) receives second European Commission approval for the treatment of adults with relapsed\/refractory follicular lymphoma<https:\/\/ir.genmab.com\/news\u2010releases\/news\u2010release\u2010details\/tepkinlyr\u2010epcoritamab\u2010receives\u2010second\u2010european\u2010commission> (2024). Accessed December 2 2025."},{"key":"e_1_2_11_3_1","volume-title":"Tepkinly [summary of product characteristics]","year":"2024"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(24)00166-2"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01725"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15996"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02410-8"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.758"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-2247"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-147937"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2203478"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol32040198"},{"key":"e_1_2_11_13_1","volume-title":"EPKINLY [prescribing information]","year":"2024"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2025.2525983"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-024-01464-2"},{"key":"e_1_2_11_16_1","volume-title":"Applied Survival Analysis: Regression Modeling of Time to Event Data","author":"David W.","year":"2008"},{"key":"e_1_2_11_17_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2021"},{"key":"e_1_2_11_18_1","volume-title":"NONMEM 7.5 Users Guides","author":"Beal S.L.","year":"1989"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-024-02985-9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2025.102974"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03175"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206913"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70362","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70362","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70362","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T03:16:21Z","timestamp":1783912581000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cpt.70362"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70362","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"2026-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}