Phase 2 Study of Daratumumab in Relapsed/Refractory Mantle-Cell Lymphoma,Diffuse Large B-Cell Lymphoma,and Follicular Lymphoma |
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| Affiliation: | 1. Hématologie, Hospices Civils de Lyon and Université de Lyon, Lyon, France;2. Department of Medicine, University of Washington, Seattle, WA;3. Department of Hematology, UMC Utrecht Cancer Center, Utrecht, The Netherlands;4. Agilent Technologies Inc, Carpinteria, CA;5. Janssen Research & Development, Raritan, NJ;6. Division of Cancer Medicine, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX;1. Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada;2. Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada;3. Division of Hematology/Oncology, St. Michael''s Hospital, University of Toronto, Toronto, Canada;1. Stanford University School of Medicine, Stanford, CA;2. The Ohio State University Comprehensive Cancer Center, Columbus, OH;3. Leeds Cancer Centre, St. James''s Institute of Oncology, Leeds, United Kingdom;4. Hofstra Northwell School of Medicine, Hempstead, NY;5. Wilmot Cancer Institute, University of Rochester Cancer Center, Rochester, NY;6. King''s College Hospital, National Health Service Foundation Trust, London, United Kingdom;7. Medical University of Lodz, Lodz, Poland;8. Moores Cancer Center, University of California San Diego, La Jolla, CA;9. Oxford National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom;10. Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain;11. Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY;12. The University of Texas MD Anderson Cancer Center, Houston, TX;13. University College Hospital Galway, Galway, Ireland;14. Università Vita-Salute San Raffaele and Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy;15. Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA;16. Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA;1. Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, China;2. State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, China;1. Unit of Lymphoid Malignancies, Department of Onco-Hematology, Milan, Italy;2. Vita-Salute San Raffaele University, Pathology Unit, Milan, Italy;3. San Raffaele Scientific Institute, Milan, Italy;4. Centro Trapianti e Terapie Cellulari “Carlo Melzi”, A O Universitaria S. Maria Misericordia, Udine, Italy;5. Division of Hematology, Spedali Civili, Brescia, Italy;6. Division of Medical Oncology, National Cancer Institute, Aviano, Italy;7. Division of Hematology, University Sapienza, Rome, Italy;8. Azienda Ospedaliera Università Senese, Siena, Italy;9. Division of Hematology, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy;10. Division of Hematology, San Bortolo Hospital, Vicenza, Italy;11. Division of Hematology, Niguarda Hospital, Milan, Italy;12. Division of Hematology, Azienda Ospedaliera di Padua, University of Padua, Italy;13. Celgene, San Diego, CA, USA;14. Department of Oncology and Hematology; G. da Saliceto Hospital, Piacenza, Italy;15. U O di Oncologia ed Ematologia Oncologica, Ospedale di Mirano, Mirano, Italy;p. University Centre for Statistics in the Biomedical Sciences (CUSSB), Vita-Salute San Raffaele University, Milano, Italy;1. Memorial Sloan Kettering Cancer Center, New York, NY, USA;2. Icahn School of Medicine at Mount Sinai, New York, NY, USA;3. University Hospital Vall d''Hebron, Vall d''Hebron Institute of Oncology (VHIO), Barcelona, Spain;4. Department of Hematology, Hospital Clínic, Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Barcelona, Spain;5. Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel;6. Department of Hematology, Koç University School of Medicine, Istanbul, Turkey;7. Chaim Sheba Medical Centre, Tel-Hashomer, Israel;8. Ankara University School of Medicine, Ankara, Turkey;9. Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;10. Hospital Clínico Universitario de Salamanca, Salamanca, Spain;11. Medical University of Gdansk, Gdansk, Poland;12. Flinders Medical Centre and Flinders University, Adelaide, SA, Australia;13. St Vincent''s Hospital, Sydney, NSW, Australia;14. Dokuz Eylül University, Izmir, Turkey;15. Gazi University, Ankara, Turkey;p. Rambam Health Care Campus, Haifa, Israel;q. Princess Alexandra Hospital, University of Queensland School of Medicine, Brisbane, QLD, Australia;r. Fundacion Jimenez Diaz University Hospital, Madrid, Spain;s. Wroclaw Medical University, Wroclaw, Poland;t. Bristol-Myers Squibb, Lawrenceville, NJ, USA;u. Janssen R&D, Spring House, PA, USA;v. Janssen R&D, Beerse, Belgium;w. Janssen R&D, San Diego, CA, USA;x. Janssen R&D, Raritan, NJ, USA;y. Department of Hematology, Jagiellonian University, Krakow, Poland;1. University of California, San Francisco, CA;2. Talon Therapeutics, South San Francisco, CA;3. The Institute of Cancer Research, Royal Cancer Hospital, London, UK |
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| Abstract: | BackgroundDaratumumab is a CD38 monoclonal antibody approved for treating relapsed/refractory and newly diagnosed multiple myeloma. Preclinical daratumumab studies demonstrated cytotoxic activity and reduced tumor growth in B-cell non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle-cell lymphoma (MCL).Patients and MethodsThis was a phase 2, open-label, multicenter, 2-stage trial. Patients with relapsed/refractory DLBCL, FL, or MCL with ≥ 50% CD38 expression were eligible for stage 1. Daratumumab (16 mg/kg; 28-day cycles) was administered intravenously weekly for 2 cycles, every 2 weeks for 4 cycles, and every 4 weeks thereafter. Overall response rate was the primary end point. Pharmacokinetic and safety were also evaluated. Stage 2 was planned to further assess daratumumab in larger populations of NHL subtypes if futility criteria were not met. The study was registered with ClinicalTrials.gov (NCT02413489).ResultsThe trial screened 138 patients resulting in accrual of 15 patients with DLBCL, 16 with FL, and 5 with MCL. Median CD38 expression across treated patients was 70%. Overall response rate was 6.7%, 12.5%, and not evaluable in DLBCL, FL, and MCL cohorts, respectively. The most common grade 3/4 treatment-emergent adverse event was thrombocytopenia (11.1%), and 4 (11.1%) patients discontinued treatment because of treatment-emergent adverse events. Infusion-related reactions occurred in 72.2% of patients (3 patients with grade 3; no grade 4).ConclusionIn NHL, the safety and pharmacokinetics of daratumumab were consistent with myeloma studies. Screen-fail rates were high, prespecified futility thresholds were met in 2 cohorts, and the study was terminated. Studies in other hematologic malignancies and amyloidosis are ongoing. |
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| Keywords: | CD38 DLBCL FL MCL Non-Hodgkin lymphoma |
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