Yvonne A Efebera, MD

Yvonne Efebera

College

College of Medicine

Department/Division

Internal Medicine

Academic Title

Assoc Professor - Clinical

Research Program

Leukemia Research

Research Interest

Multiple Myeloma, Graft vs Host Disease, Paraproteinemias, Amyloidosis, Necrobiotic Xanthogranuloma

The development of osteolytic bone disease in Multiple Myeloma (MM) is the result of increased osteoclastic bone resorption and impairment of osteoblastic bone formation. The Wnt signaling pathway is important for osteoblastic differentiation. Dickkopf (DKK1), a Wnt inhibitor, inhibits osteoblast activity, and its serum level directly correlates with increased bone lesions in newly diagnosed MM. BHQ880, an IgG1 anti DKK1 monoclonal antibody that has been shown in vitro to neutralize DKK1 and activate the Wnt pathway, thus enhancing osteoblastic activity and differentiation and improving bone disease. BHQ880 may also inhibit myeloma cell growth. We propose to perform a phase I dose determination study followed by a randomized, placebo controlled, double blind phase II study of BHQ880 with/without zoledronic acid in multiple myeloma patients undergoing autologous and allogeneic transplant. To determine effect of BHQ880 on prevention of progression of bone disease. We plan to assess: A: The maximum tolerated dose and to characterize Dose limiting toxicity of escalating doses of BHQ880 in combination with zoledronic acid. B: to characterize the binding kinetics of DKK-1/BHQ880 complex in serum and characterize serum DKK1 levels during treatment. C: The pharmacodynamics of BHQ880 by measuring biochemical markers of bone formation (osteocalcin, bone specific alkaline phosphatase, P1NP, DEXA scan) resorption (serum CTX, urine NTX, Trap 5b) and metabolism (RANKL, OPG) in serum and urine D: Assess the effect of BHQ880 on calcium and phosphate metabolism Hypothesis: We hypothesize that the combination of BHQ880 with zoledronic acid will be well tolerated, will enhance osteoblast activity and differentiation improving or preventing further bone disease, will increase bone formation markers and will decrease DKK-1 expression.


Education and Background

Education

  • MD, Pennsylvania State University

    Hershey, PA (USA)

Residencies

  • Hematology Research Training Grant

    Boston University Medical Center

    Boston, MA (USA)

  • Residency, Internal Medicine

    Cleveland Clinic Foundation

    Cleveland, OH (USA)

Fellowship

  • Clinical and Research Fellowship, Stem Cell and Marrow Transplantation

    University of Texas, MD Anderson Cancer Center

    Houston, TX (USA)

  • Fellowship, Hematology/Oncology

    Boston University Medical Center

    Boston, MA (USA)

Office Location

A346 Starling Loving Hall

320 W 10th Ave, Columbus, OH 43210


614-293-2268

614-366-5970



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