TY - JOUR
T1 - Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma
AU - Timmerman, John
AU - Herbaux, Charles
AU - Ribrag, Vincent
AU - Zelenetz, Andrew D.
AU - Houot, Roch
AU - Neelapu, Sattva S.
AU - Logan, Theodore
AU - Lossos, Izidore S.
AU - Urba, Walter
AU - Salles, Gilles
AU - Ramchandren, Radhakrishnan
AU - Jacobson, Caron
AU - Godwin, John
AU - Carpio, Cecilia
AU - Lathers, Deanne
AU - Liu, Yali
AU - Neely, Jaclyn
AU - Suryawanshi, Satyendra
AU - Koguchi, Yoshinobu
AU - Levy, Ronald
N1 - Funding Information:
S. Neelapu: Advisory board member and/or consultant for Kite/Gilead, Merck, Celgene, Novartis, Unum Therapeutics, Pfizer, Precision BioSciences, Cell Medica, Allogene, Incyte, and Legend Biotech; research funding from Kite/Gilead, Merck, Bristol‐Myers Squibb, Cellectis, Poseida, Karus, Acerta, and Unum Therapeutics.
Funding Information:
J. Timmerman: Advisory board member and/or consultant for Celgene, Kite/Gilead, Partner Therapeutics, and TeneoBio; research funding from Bristol‐Myers Squibb, Kite/Gilead, Merck, and Spectrum Pharmaceuticals.
Funding Information:
T. Logan: Advisory board member and/or consultant for Prometheus; research funding from Abbott, Abraxis, Acceleron, Amgen, Argos, AstraZeneca, Aveo, BioVex, Bristol‐Myers Squibb, Cerulean, Dynavax, Eisai, EMD Serono, GlaxoSmithKline, Iovance Biotherapeutics, Immatics, Lilly, MacroGenics, Millennium, MedImmune, Merck, Novartis, Peloton, Pfizer, Prometheus, Roche, Synta, Threshold, and Tracon.
Funding Information:
Y. Koguchi: Research funding from Bristol‐Myers Squibb, Shimadzu Corporation, and Tesaro, a GlaxoSmithKline company.
Funding Information:
V. Ribrag: Advisory board member and/or consultant for MSD, Bristol‐Myers Squibb, Epizyme, Nanostring, Pharmamar, Servier, Gilead; research funding from ArgenX, AstraZeneca, Bristol‐Myers Squibb, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, and Sanofi; personal fees from Roche and Infinity; non‐financial support from AstraZeneca, Bayer, Bristol‐Myers Squibb, Boehringer Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck, NH TherAguix, Pfizer, and Roche.
Funding Information:
This study was supported by Bristol-Myers Squibb, Princeton, NJ. We thank the patients and their families and the investigators and research staff at all study sites. We also thank Franck Morschhauser from the Centre Hospitalier R?gional Universitaire de Lille in Lille, France, for his contributions. Editorial assistance was provided by Jillian Brechbiel, PhD, and Kathleen Covino, PhD, of Chrysalis Medical Communications, Inc, Hamilton, NJ, and was funded by Bristol-Myers Squibb.
Funding Information:
R. Levy: Scientific advisory board for Five Prime, Corvus, Quadriga, BeiGene, GigaGen, TeneoBio, Sutro, Checkmate, Nurix, Dragonfly, Innate Pharma, Abpro, Apexigen, Nohla, Spotlight, Forty Seven Inc, xCella, Immunocore, and Walking Fish; research funding from Pfizer, Bristol‐Myers Squibb, and Pharmacyclics.
Funding Information:
W. Urba: Advisory board member for AstraZeneca; research funding from Bristol‐Myers Squibb.
Publisher Copyright:
© 2020 Wiley Periodicals, Inc.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.25757
DO - 10.1002/ajh.25757
M3 - Article
C2 - 32052473
AN - SCOPUS:85081223351
VL - 95
SP - 510
EP - 520
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
IS - 5
ER -