Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma Journal Article


Authors: Timmerman, J.; Herbaux, C.; Ribrag, V.; Zelenetz, A. D.; Houot, R.; Neelapu, S. S.; Logan, T.; Lossos, I. S.; Urba, W.; Salles, G.; Ramchandren, R.; Jacobson, C.; Godwin, J.; Carpio, C.; Lathers, D.; Liu, Y.; Neely, J.; Suryawanshi, S.; Koguchi, Y.; Levy, R.
Article Title: Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma
Abstract: Urelumab, a fully human, non-ligand binding, CD137 agonist IgG4 monoclonal antibody, enhances T-cell and natural killer-cell antitumor activity in preclinical models, and may enhance cytotoxic activity of rituximab. Here we report results in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other B-cell lymphomas, in phase 1 studies evaluating urelumab alone (NCT01471210) or combined with rituximab (NCT01775631). Sixty patients received urelumab (0.3 mg/kg IV Q3W, 8 mg IV Q3W, or 8 mg IV Q6W); 46 received urelumab (0.1 mg/kg, 0.3 mg/kg, or 8 mg IV Q3W) plus rituximab 375 mg/m2 IV QW. The maximum tolerated dose (MTD) of urelumab was determined to be 0.1 mg/kg or 8 mg Q3W after a single event of potential drug-induced liver injury occurred with urelumab 0.3 mg/kg. Treatment-related AEs were reported in 52% (urelumab: grade 3/4, 15%) and 72% (urelumab + rituximab: grade 3/4, 28%); three led to discontinuation (grade 3 increased AST, grade 4 acute hepatitis [urelumab]; one death from sepsis syndrome [urelumab plus rituximab]). Objective response rates/disease control rates were 6%/19% (DLBCL, n = 31), 12%/35% (FL, n = 17), and 17%/42% (other B-cell lymphomas, n = 12) with urelumab and 10%/24% (DLBCL, n = 29) and 35%/71% (FL, n = 17) with urelumab plus rituximab. Durable remissions in heavily pretreated patients were achieved; however, many were observed at doses exceeding the MTD. These data show that urelumab alone or in combination with rituximab demonstrated manageable safety in B-cell lymphoma, but the combination did not enhance clinical activity relative to rituximab alone or other current standard of care. © 2020 Wiley Periodicals, Inc.
Journal Title: American Journal of Hematology
Volume: 95
Issue: 5
ISSN: 0361-8609
Publisher: John Wiley & Sons, Inc.  
Date Published: 2020-05-01
Start Page: 510
End Page: 520
Language: English
DOI: 10.1002/ajh.25757
PUBMED: 32052473
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Andrew D Zelenetz
    600 Zelenetz