Multiple myeloma is a blood cancer that typically affects those aged 70 years and older. Although considered an uncommon disease, the American Cancer Society estimates that in 2015, 26,850 new cases will be diagnosed in the United States this year. Global studies show a worldwide incidence of 86,000 cases per year.
The high five-year patient survival rate makes this type of cancer an ideal target for research and treatment studies. Pharmaceutical companies have also embraced the search for treatment of multiple myeloma, since the availability of a successful therapy would enable patients to live significantly improved and productive lives.
As the number of multiple myeloma clinical trials continue to increase, variability in testing results has become a challenge. As a result, many pharmaceutical companies are turning to central laboratories for feasible solutions to reduce this variability.
The known culprit of multiple myeloma is an abnormal plasma cell. When plasma cells become cancerous, they increase by number in bone marrow, tissues or even the circulation. Most abnormal plasma cells keep the capability to produce immunoglobulins, which may have two identical heavy and two identical light chains, or can be formed by only light or heavy chains. Regardless of their structure, these immunoglobulins do not protect the body. Abnormal immunoglobulins are known as M-proteins, or monoclonal proteins, and may be present in large amounts in the circulation and can even be excreted in the urine.
Multiple myeloma is part of a group of diseases associated with abnormal plasma cells. These diseases are known as plasma cell dyscrasias. Therefore, finding abnormal plasma cells and/or an M-protein does not imply an immediately diagnosis of multiple myeloma. A multiple myeloma diagnosis is based on criteria that includes clinical, imaging and laboratory parameters. Among the laboratory diagnostic tools currently available, three tests remain as essential components in the laboratory testing for multiple myeloma clinical trials: protein electrophoresis (PEP), a well-established test performed in serum (SPEP) and urine (UPEP); protein immunofixation; and free light chain.
Most multiple myeloma patients are followed several years throughout their disease. Clinicians monitor the changes of SPEP, UPEP and the free light chain ratio - all of which are considered key disease markers. The top challenge posed by this approach is the markers' biological variability.
Variability can also occur during the pre-analytical phase. Laboratories throughout the world can each have slightly different specimen collection, tube type, preservative, transportation and/or storage instructions. For example, while free light chain reagents are produced by the same manufacturer, analysis may be performed by different instruments. Conversely, PEP and IFE reagents are produced by several different manufacturers. The PEF and IFE assays are also complex, including many individual steps that could each produce differences when specimens are tested in different laboratories.
With different PEP and IFE methods in use, sources of variability can combine and produce even greater differences. Furthermore, variability may conceal imperfectly identified source patients and/or incorrect type specimens. Finally, variability becomes even a greater challenge in the clinical trial arena, where many countries and multiple locations are the norm.
Covance Central Laboratory Services responded to the increasing variability in multiple myeloma testing by creating a dedicated multiple myeloma Team that performs all PEP, IFE and free light chain testing "under one roof," performing all tests via a centralized approach.
We use the same assays and instruments worldwide for each PEP and IFE we conduct, plus all PEP and IFE reports follow the same format, which is easily fit for data transfer. For greater consistency, each multiple myeloma case is reviewed by our Indianapolis team. Whenever there is a question, our three on-site pathologists are consulted. In addition, all screening cases are reviewed by one of our on-site pathologists. PEP and IFE studies are kept in a personal file for each patient. Those files are pulled and compared to incoming patient specimens. Incorrect source patients may be discoverable based on the location of the myeloma peak within the PEP waveform and on IFE findings. If any discrepancy is found, appropriate communication with the investigator site is conducted in order to ensure the delivery of optimal laboratory data. All these steps have tremendously decreased result variability for our sponsors.
Free light chains are also performed by the same instrument and assay globally. The information from the free light chain results is available to the Myeloma Team when PEP and IFE's are read and interpreted.
In addition to our standardized multiple myeloma testing approach, Covance has also addressed the pre-analytical testing aspects. This includes uniform specimen collection, tube type, preservatives and storage instructions. The 24-hour urine samples for PEP and IFE can represent a challenge for the site because patients mostly collect them at home. Therefore, we include written instructions on the collecting urine jugs on what to do before, during and after collection. Lastly, detailed instructions are greatly emphasized on all Covance investigator manuals provided to sites globally.
Your choice in selecting a central lab can have a significant impact on the success of your Multiple Myeloma studies. Our approach to reducing the variability in multiple myeloma testing is just one example of how we go above and beyond to ensure globally combinable data and high-quality results.
Click here for a more in-depth overview of multiple myeloma and how it's diagnosed, including the measurement, quantification and classification of the M-protein.