Two novel therapies for multiple myeloma

Mar 14 2007

Two novel biologics are currently being investigated for their potential benefit to multiple myeloma patients in separate ongoing clinical trials at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

A Phase 2 trial with VEGF Trap will assess the drug's ability to slow tumor growth in patients with multiple myeloma. VEGF Trap is a recombinant human fusion protein that binds VEGF, a key molecule in tumor blood-vessel growth (angiogenesis).

A Phase 1 trial of hLL1 (anti-CD74), a humanized monoclonal antibody that has shown significant growth inhibition of multiple myeloma and B-lymphoma cells in preclinical studies, and whose mechanism of action is associated with inducing apoptosis (cell death), will be studied for safety and dosage.

"These two exciting antibody trials may give new hope to myeloma patients with relapsed and refractory disease," says Dr. Ruben Niesvizky, director of NewYork-Presbyterian/Weill Cornell's Multiple Myeloma Program and principal investigator of both studies. He is associate professor of medicine at Weill Cornell Medical College.

NewYork-Presbyterian/Weill Cornell and others have shown that myeloma growth is highly dependent on VEGF (vascular endothelial growth factor) and that blood-vessel growth (angiogenesis) is a fundamental aspect of myeloma tumor growth.

VEGF Trap works by binding VEGF more tightly than the body's own receptors that mediate the angiogenic activity of VEGF.

The drug hLL1 (IMMU-115) represents the first antibody exploiting the high expression of the CD74 molecule (an invariant chain marker associated with HLA antigens) in myeloma cells. This molecule not only plays a role in immunity, but has also been shown to have direct signaling effects in hematopoietic tumors. NewYork-Presbyterian/Weill Cornell is the first to begin evaluation of this new antibody as a therapy for any disease.

The studies are open to patients with relapsed or refractory multiple myeloma. Fifty patients will be recruited for the VEGF Trap study at centers representing the New York Consortium (NewYork-Presbyterian/Weill Cornell, NewYork-Presbyterian Hospital/Columbia University Medical Center, Mount Sinai and North Shore University Hospital). Approximately 35 patients will be recruited for the hLL1 study at Weill Cornell, and several other trial sites of the Multiple Myeloma Consortium.

The drug hLL1 is developed by Immunomedics of Morris Plains, N.J.; the company is funding the study of its drug. VEGF Trap is being developed in a collaboration between Regeneron Pharmaceuticals of Tarrytown, N.Y. and Sanofi-Aventis USA, of Bridgewater, New Jersey; the study is sponsored by the National Cancer Institute's Cancer Therapy Evaluation Program (NCI/CTEP) under a Clinical Trials Agreement between Sanofi-Aventis and NCI; and conducted under the NCI's Division of Cancer Treatment and Diagnosis Investigational New Drug Application for VEGF Trap.

The Multiple Myeloma Program at NewYork-Presbyterian/Weill Cornell, one of the three largest such centers in the U.S., takes an aggressive and multidisciplinary approach—offering programs for transplants, vaccine development and drugs, as well as clinical research trials for all stages of the disease. The Myeloma Program is also enrolling for other investigational drug therapies. The Program engages in collaborative work in translational medicine with Weill Cornell's Dr. Shahin Rafii and Dr. Selina Chen-Kiang, as well as with Dr. Roger Pearse.

Multiple myeloma is a blood cancer that causes white blood cells to become malignant and attack the body's bones, resulting in painful fractures, kidney failure and death. The disease affects an estimated 40,000 Americans. From 1973 to 1999, the U.S. has seen a 35 percent increase in multiple-myeloma deaths; these numbers are rising for reasons that are not understood.

Co-investigators for the VEGF Trap study include NewYork-Presbyterian/Weill Cornell's Drs. Jia Ruan, Roger Pearse and Morton Coleman; NewYork-Presbyterian/Columbia's Ajai Chari; and investigators representing the other members of the New York Consortium. Statistical analysis will be provided by Weill Cornell's Dr. Madhu Mazumdar. Co-investigators for the hLL1 study include Weill Cornell's Drs. Scott Ely and John Leonard.