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Hematologist, Multiple Myeloma Specialist, VU University Medical Center Amsterdam
Clinical Program Leader & Director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana Farber
Founder and Leader of the Clinical Research Unit, Dept of Hematology, Vejle Hospital
Director, Michele & Stephen Kirsch Laboratory, Dana-Farber Cancer Institute
Medical Oncologist and Translational Researcher, University of Cincinnati Cancer Institute
Chair of Hematology and Professor of Medicine at Mayo Clinic
Director of Plasma Cell Disorder Program, Levine Cancer Institute/Carolinas Healthcare System
Chief, Hematological Malignancies & Bone Marrow Transplantation, BIDMC
Senior Fellow, Jerome Lipper Multiple Myeloma Center, Dana Farber
Professor of Medicine, Hematology at Mayo Clinic
Assistant Professor in Medicine, Medical Oncology, Dana-Farber Cancer Institute
Hematologist-Oncologist, Center for Multiple Myeloma, MGH
Internal medicine resident, Ohio State University
Hematology & Oncology Fellow, Taussig Cancer Institute, Cleveland Clinic
Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1–2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.
In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics.
No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months.
Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288.)
Hematologist, Multiple Myeloma Specialist, VU University Medical Center Amsterdam
Clinical Program Leader & Director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana Farber
Founder and Leader of the Clinical Research Unit, Dept of Hematology, Vejle Hospital
Director, Michele & Stephen Kirsch Laboratory, Dana-Farber Cancer Institute
Medical Oncologist and Translational Researcher, University of Cincinnati Cancer Institute
Chair of Hematology and Professor of Medicine at Mayo Clinic
Director of Plasma Cell Disorder Program, Levine Cancer Institute/Carolinas Healthcare System
Chief, Hematological Malignancies & Bone Marrow Transplantation, BIDMC
Senior Fellow, Jerome Lipper Multiple Myeloma Center, Dana Farber
Professor of Medicine, Hematology at Mayo Clinic
Assistant Professor in Medicine, Medical Oncology, Dana-Farber Cancer Institute
Hematologist-Oncologist, Center for Multiple Myeloma, MGH
Internal medicine resident, Ohio State University
Hematology & Oncology Fellow, Taussig Cancer Institute, Cleveland Clinic