NYUCI researchers are investigating the fundamental biology of multiple myeloma and developing and assessing new therapies for this disease. Our goal is to improve the outcome of patients with multiple myeloma using targeted therapies that will have greater effectiveness and fewer side effects than conventional approaches.
We have one of the most vigorous translational research programs in the New York City area for multiple myeloma, with basic science studies leading to the development of new treatments that are assessed in patients. Likewise, clinical observations in patients are informing new avenues of laboratory inquiry. The NYUCI offers clinical trials for patients with all stages of multiple myeloma: asymptomatic patients, those initiating treatment, and those experiencing a recurrence.
Novel Targeted Drugs and Drug Combinations
There is evidence that folate metabolism is important to growth and survival in multiple myeloma. NYUCI laboratory scientists are studying the response of folate genes to treatment with pralatrexate, a drug approved for the treatment of peripheral T-cell lymphoma that interferes with this process. NYUCI investigators were leaders in the assessment of pralatrexate for lymphoma and have a great deal of knowledge and experience with this drug. Laboratory studies indicate the multiple myeloma cells can be killed with pralatrexate. Animal studies are under way to examine the drug's effects on multiple myeloma in vivo.
The goal is to open a clinical trial of pralatrexate in multiple myeloma patients to see how folate gene expression might predict a patient's response to the drug. This effort is part of a broader initiative at the NYUCI to examine the genetics of each multiple myeloma patient's bone marrow to determine which patients would benefit most from particular drugs. This approach is part of a growing trend in cancer therapy called personalized medicine.
NYUCI scientists are also trying to understand how multiple myeloma cells differ from normal plasma cells at the molecular level. They are examining signaling pathways for the proteins JAK, STAT, and Ras and determining the roles of these proteins in the resistance to anticancer drugs that most patients with myeloma eventually develop. Our clinical investigators are using the information gleaned from these studies to evaluate drugs that may be used in combination with bortezomib or lenalidomide to overcome this resistance. Examples include:
- Drugs that target pathways involved in endoplasmic reticulum stress, thereby mediating bortezomib resistance.
- HDAC inhibitors, such as vorinostat, which modulate the expression of genes involved in drug resistance; HDAC inhibitors may be used in combination with bortezomib or lenalidomide to restore the sensitivity of multiple myeloma cells to these drugs.
- Drugs that inhibit the repair of DNA in cancer cells damaged by chemotherapy; blocking cancer cell DNA repair may restore their sensitivity to anticancer drugs, such as melphalan. Bortezomib inhibits DNA repair and may work more effectively when given with melphalan, the chemotherapy drug most often used to treat multiple myeloma.
- Signal transduction inhibitors may also be useful for mobilizing stem cells prior to stem cell transplantation.
NYUCI researchers are searching for ways to modulate the immune system to fight multiple myeloma. Immunomodulatory drugs (ImiDs) are believed to work in part by stimulating the patient's immune system to attack and destroy myeloma cells. Examples include:
- lenalidomide in combination with other drugs, including carfilzomib (which works in a manner similar to bortezomib, but with fewer side effects)
- investigational drugs such as pomalidomide given with vorinostat, a combination which has promise in clinical trials in patients with relapsed disease.
NYUCI investigators are also assessing therapies for asymptomatic myeloma in clinical trials, to delay the onset of active multiple myeloma. One example is TBL-12, a sea cucumber extract (taken by mouth) already available as a food supplement that may modulate the immune system. This is already showing some effects in an early phase. Another is IPH2101, a fully human monoclonal antibody against a protein called KIR. The NYUCI is the only center in New York City offering these studies.
Investigators are also assessing approaches to manipulate stem cells and regulatory T cells to induce an antitumor effect. The immunologically altered stem cells would be returned to the patient as part of the stem cell transplant to enhance the effectiveness of the transplant. The NYUCI is currently developing an enhance stem cell facility that would permit both autologous and allogeneic stem cell transplantation.