State-of-the-art Research Committed to the Treatment of Multiple Myeloma and Amyloidosis

Multiple Myeloma and Amyloidosis Program at Columbia

Principal Investigator

The Lentzsch Laboratory focuses on the identification of novel targets for the treatment of Multiple Myeloma, Multiple Myeloma bone disease, and AL amyloidosis. Our work demonstrated that the translation initiation factor eIF4E level is aberrantly elevated in multiple myeloma cells, and targeting against protein translational machinery represents a novel therapy that inhibits multiple myeloma cell growth and induces myeloma cell apoptosis. Our investigation on the mechanism that activates osteoclasts led to the identification of matrix metalloproteinase 13 (MMP-13) as a critical inducer of osteolysis.

Our research on the understanding of the pathobiology underlying the mechanisms of immunomodulatory derivatives of thalidomide (IMiDs) in multiple myeloma and their effects on hematopoietic stem cells helped to delineate the risk factors contributing to secondary primary malignancies associated with IMiD treatments.

Furthermore, our innovative research in amyloidosis resulted in a series of translational clinical trials such as establishing new treatments for relapsed AL amyloidosis in a multi-center trial investigating bendamustine. Currently, in a FDA funded phase 1 trial, we are investigating whether the monoclonal antibody 11-1F4, targeting directly amyloid fibrils, can break down amyloid and subsequently improve organ function in amyloid patients. In addition, we designed and developed bi-specific antibodies, which target well-identified macrophage/neutrophil cell surface markers as well as AL Amyloid, to enhance amyloid elimination.