Impact of Daratumumab Monotherapy on Bone Parameters in Patients with Relapsed and/or Refractory Multiple Myeloma Who Have Received at Least 2 Prior Lines of Therapy Including Lenalidomide and a Proteasome Inhibitor; Interim Analysis of a Phase 2 Study (the REBUILD Study)
Introduction: A major clinical feature of multiple myeloma (MM) is osteolytic bone disease, with bone resorption prevailing bone formation. Daratumumab, an IgG1κ human monoclonal antibody that targets CD38, has been licensed for use in patients (pts) with relapsed or refractory MM (RRMM); however, its effect on bone disease has not yet been determined in a clinical setting. CD38 expression has been associated with osteoclast formation and bone resorption in in vitro studies and treatment with daratumumab has demonstrated an inhibitory effect on osteoclastogenesis. This study aims to evaluate the impact of daratumumab monotherapy on biochemical markers of bone metabolism in RRMM pts.
Conclusions: Regarding the primary endpoint of the REBUILD study, results from this interim analysis indicate that daratumumab monotherapy decreases TRACP-5b levels, which was more pronounced in responders, but this is not accompanied by a reduction in CTX. An effect on CTX levels may become evident with additional follow-up. However, a clear increase in serum levels of all markers of bone formation tested (bALP, OC, PINP) was observed, especially among responders, which might at least partially be explained by a reduction of the osteoblast inhibitors sclerostin and DKK-1. Thus, daratumumab monotherapy in this RRMM population (heavily pre-treated pts with multiple lytic bone lesions and limited use of bisphosphonates) results in a decrease in TRACP-5b and osteoblast inhibitors and an increase in bone formation markers, suggesting an overall positive impact on bone remodeling. The study is ongoing and updated results will be presented at the meeting.
ABOUT EVANGELOS TERPOS, MD, PhD
Evangelos Terpos, MD, PhD, is an Associate Professor of Hematology, in the Department of Clinical Therapeutics at the University of Athens, School of Medicine. Dr. Terpos is co-chair of the Bone Subgroup of the International Myeloma Working Group and the Guideline Subgroup of the European Myeloma Network. He is a reviewer of scientific papers in more than 50 medical journals and has reviewed abstracts for ASH, EHA & EBMT meetings. He is a member of the editorial board of Haematologica. Visit Dr. Evangelos Terpos’ full biography.