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

  • Am J Hematol. 2020 May;95(5):510-520. doi: 10.1002/ajh.25757.
John Timmerman  1 ,  Charles Herbaux  2 ,  Vincent Ribrag  3 ,  Andrew D Zelenetz  4 ,  Roch Houot  5  6 ,  Sattva S Neelapu  7 ,  Theodore Logan  8 ,  Izidore S Lossos  9 ,  Walter Urba  10 ,  Gilles Salles  11 ,  Radhakrishnan Ramchandren  12 ,  Caron Jacobson  13 ,  John Godwin  10 ,  Cecilia Carpio  14 ,  Deanne Lathers  15 ,  Yali Liu  15 ,  Jaclyn Neely  15 ,  Satyendra Suryawanshi  15 ,  Yoshinobu Koguchi  10 ,  Ronald Levy  16
Affiliations
  • 1. UCLA Medical Center, Los Angeles, California.
  • 2. Centre Hospitalier Régional Universitaire de Lille, Lille, France.
  • 3. Institut Gustave Roussy, Villejuif, France.
  • 4. Memorial Sloan Kettering Cancer Center, New York, New York.
  • 5. CHU Rennes, Service Hématologie Clinique, Rennes, France.
  • 6. INSERM, Unité d'Investigation Clinique, Rennes, France.
  • 7. The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 8. Simon Cancer Center, Indiana University, Indianapolis, Indiana.
  • 9. University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida.
  • 10. Earle A. Chiles Research Institute, Providence Cancer Center, Portland, Oregon.
  • 11. Hospices Civils de Lyon, Université de Lyon, Lyon, France.
  • 12. Karmanos Cancer Institute, Detroit, Michigan.
  • 13. Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
  • 14. Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • 15. Bristol-Myers Squibb, Princeton, New Jersey.
  • 16. Stanford University School of Medicine, Stanford, California.
PMID: 32052473 DOI: 10.1002/ajh.25757
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.

Products