Dr. Vorhees
Peter Voorhees, MD
Plasma Cell Disorders Program
Department of Hematologic Oncology and Blood Disorders
Levine Cancer Institute
Atrium Health
MedicalResearch.com: What is the background for this study?
Response: All multiple myeloma arises from its precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Although the rate of progression to multiple myeloma for patients with MGUS is low (~5% over 5 years), patients with SMM have a ~50% likelihood of requiring therapy for their multiple myeloma within the first 5 years of diagnosis. For those at intermediate to high risk of disease progression, early intervention to delay progression of disease, thereby averting disease-related morbidities related and potentially changing the natural course of the disease, is highly desirable.
On the other hand, given the fact that these patients are by definition asymptomatic and would otherwise be monitored off treatment, it is critical that any intervention applied in this group of patients is well tolerated. Daratumumab is a highly attractive candidate in this particular space, because it has single agent activity in heavily-pretreated relapsed/refractory multiple myeloma and a favorable side effect profile relative to many other myeloma therapeutics. Additionally, given the importance of impaired immune surveillance in multiple myeloma, the immuno-stimulatory effects of daratumumab in the bone marrow microenvironment could potentially reawaken robust T cell responses to the disease.
MedicalResearch.com: What are the main findings?
Response: The CENTAURUS study was a randomized phase II trial evaluating 3 different dosing schedules of daratumumab for the treatment of smoldering multiple myeloma at intermediate to high risk of progression to active disease. Patients either received 8 weekly doses (short arm), 8 weekly doses followed by once every 8-week dosing for 19 additional 8-week cycles (intermediate arm) or 8 weekly doses followed by every 2-week dosing for 16 weeks, every 4-week dosing for 32 weeks and then once every 8-week dosing for an additional 13 8-week cycles (intense arm). Importantly, the overall response rate was 56% (27% PRs, 24% VGPRs, 5% CRs/sCRs) and the 24-month progression free survival (progression from SLiM - CRAB criteria of multiple myeloma) was 90% in the intense arm compared with 75% in the short arm. When considering biochemical progression and SLiM - CRAB criteria, the 24-month progression-free survival was 78% for the intense arm, 27% for the short arm. Serious adverse events related to daratumumab occurred in only 2 of 142 patients and only 2 patients discontinued treatment due to daratumumab-related adverse events. Hematologic treatment-emergent adverse events occurred in
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