The development of multiple myeloma is the result of a series of progressive genetic events. One such event is the translocation of t(4;14) and the over-expression of fibroblast growth factor receptor 3 (FGFR3). These characteristics, present in approximately 25% of multiple myeloma cell lines and 16% of patients, are known to be a poor prognostic indicator for multiple myeloma.

Drugs that are active against FGFR3 are now being tested in the laboratory and will likely enter clinical trials soon.

In anticipation of a Phase I clinical trial of FGFR3 inhibition in myeloma, the MMRC has initiated a pre-clinical screening and correlative sciences study, led by Principal Investigator Keith Stewart, MD, University of Toronto, to identify and validate the most sensitive and specific screening methods to detect myeloma patients who exhibit a translocation of t(4;14) and express FGFR3.

As part of this study, MMRC Member Institutions will collect additional blood and bone marrow samples of patients with multiple myeloma at the time of their clinical evaluations. All samples will be shipped with an anonymized subject identification number to the MMRC Tissue Bank at the Mayo Clinic. Upon receipt at the MMRC Tissue Bank housed at the Mayo Clinic, each sample will undergo the following analyses and processes:

• Fluorescent in Situ Hybridization (FISH)
• RT-PCR
• Immunohistochemistry
• gene expression profiling
• cell sorting
• flow cytometry
• mutation analysis
• surrogate marker assays

These tests will enable researchers validate optimal screening measure to detect myeloma patients who exhibit a translocation of t(4;14) and express FGFR3. As these characteristics confer a poor prognosis for myeloma patients, the ability to detect these genetic changes is essential in developing new and effective therapies for this subset of myeloma patients.

Screening of approximately 300 patient tissue samples is expected to identify 30 samples with a translocation of t(4;14) and over-expression of FGFR3. Patients confirmed to have this genetic profile may qualify to participate in future clinical trials exploring drug candidates active against this target.

All samples will be collected following informed consent and will be uniformly collected, shipped, processed and stored following Good Laboratory Practices (GLP) and in a manner consistent with all regulatory requirements, including the Health Insurance Portability and Accountability Act of 1996 (HIPAA).