Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma
Timmerman, John (UCLA Medical Center)
Herbaux, Charles (Centre Hospitalier Régional Universitaire de Lille)
Ribrag, Vincent (Institut Gustave Roussy (Villejuif, França))
Zelenetz, Andrew D. (Memorial Sloan Kettering Cancer Center)
Houot, Roch (Unité dʼInvestigation Clinique)
Neelapu, Sattva S. (The University of Texas MD Anderson Cancer Center)
Logan, Theodore (Indiana University)
Lossos, Izidore S. (Sylvester Comprehensive Cancer Center)
Urba, Walter (Providence Cancer Center)
Salles, Gilles (Université de Lyon)
Ramchandren, Radhakrishnan (Karmanos Cancer Institute)
Jacobson, Caron (Harvard Medical School)
Godwin, John (Providence Cancer Center)
Carpio Segura, Cecilia del Carmen (Universitat Autònoma de Barcelona. Departament de Medicina)
Lathers, Deanne (Bristol-Myers Squibb)
Liu, Yali (Bristol-Myers Squibb)
Neely, Jaclyn (Bristol-Myers Squibb)
Suryawanshi, Satyendra (Bristol-Myers Squibb)
Koguchi, Yoshinobu (Providence Cancer Center)
Levy, Ronald (Stanford University School of Medicine)

Data:	2020
Resum:	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/m 2 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.
Nota:	Altres ajuts: This study was supported by Bristol-Myers Squibb, Princeton, NJ.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	American Journal of Hematology, Vol. 95 (february 2020) , p. 510-520, ISSN 1096-8652

DOI: 10.1002/ajh.25757
PMID: 32052473

11 p, 1.4 MB

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