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.

• Authors: John Timmerman, Charles Herbaux, Vincent Ribrag, Andrew D Zelenetz, Roch Houot, Sattva S Neelapu, Theodore Logan, Izidore S Lossos, Walter Urba, Gilles Salles, Radhakrishnan Ramchandren, Caron Jacobson, John Godwin, Cecilia Carpio, Deanne Lathers, Yali Liu, Jaclyn Neely, Satyendra Suryawanshi, Yoshinobu Koguchi, Ronald Levy
• Journal: American journal of hematology (Am J Hematol) Vol. 95 Issue 5 Pg. 510-520 (05 2020) ISSN: 1096-8652 [Electronic] United States
• PMID: 32052473 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents, Immunological
• urelumab
• Rituximab

Topics

• Aged
• Antibodies, Monoclonal (pharmacokinetics, pharmacology, therapeutic use)
• Antineoplastic Agents, Immunological (pharmacology, therapeutic use)
• Female
• Humans
• Lymphoma, Large B-Cell, Diffuse (drug therapy, mortality)
• Male
• Middle Aged
• Progression-Free Survival
• Rituximab (pharmacokinetics, pharmacology, therapeutic use)