As the volume of multiple myeloma clinical trials continues to grow, additional tests are being validated in an effort to benefit patients who typically have a five-year survival rate. These dynamics are driving strategies to address variability in testing procedures and data analysis. We recently met with our dedicated Multiple Myeloma Team to learn more.
Centralized service for testing
Most multiple myeloma patients are followed several years throughout their disease. Clinicians monitor the measurement 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 marker’s biological variability.
With different protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) methods in use, sources of variability can combine and produce even greater differences. Further, variability may conceal imperfectly identified source patients and/or incorrect type specimens. Finally, variability becomes an even greater challenge in the clinical trial arena, where many countries and multiple locations are the norm.
It is for this reason that pharmaceutical companies are turning to central laboratories for feasible solutions to reduce this variability.
Centralized testing approaches, including PEP, IFE and free light chain testing, are key to bringing consistency and reliability to the results produced from myeloma studies – no matter where in the world the test samples have originated.
In addition to centralized testing approaches, our dedicated Multiple Myeloma Team provides expertise in all aspects related to sample collection and processing, laboratory testing and data interpretation and reporting. Results from the in-house free light chain assays and immunoglobulin testing are available to the myeloma team for centralized interpretation alongside PEP and IFE results.
Reliability and consistency in analyzing, interpreting and communicating data
To provide an accurate baseline we have, highly trained pathologists review first screening visits for all cases received. These pathologists, while reviewing cases directly, are also available to the wider technical team for expert consultation.
Each patient has a personal file whereby the unique case number can be identified and results are compared to incoming patient specimens: an organized, robust and confidential tracking system. Each specimen and the associated project number is verified for completeness. Test orders, such as specific tests requested, the ordering physician information and a specimen inventory are entered into our secure systems.
It is a fundamental element of the service that only technicians and pathologists who are highly trained are able to examine samples and provide interpretations. As such, technicians are required to undertake 1,000 interpretations with supervision prior to working independently. It is this central team that delivers all interpretations, with a key focus on removing ambiguity.
Confidence in the collection and processing of specimens
Variability in multiple myeloma data can also occur because 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 on 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.
In addition to addressing variability in interpretation, our Multiple Myeloma Team also addresses both the pre-analytical and analytical aspects of PEP, IFE and free light chain testing.
Protocol- and visit-specific collection kits are assembled at a central site in Indianapolis (USA) and provided to investigator sites around the world to support consistency in sample collection.
Achieving analytical consistency is also of great importance. For this reason, the same instruments, reagents, and procedures are employed throughout our Central Labs (CLS) networks. All of this equips sponsors with regional flexibility as to where studies are conducted, with the reassurance of standardized, reliable data collection and testing methodology.
The following services are offered across most of our laboratory sites around the world, with the reliability of data being interpreted centrally in Indianapolis:
- HYDRASHIFT 2/4 assays – (CLS) is the first central laboratory to offer this assay. It is especially useful for therapeutic antibody testing if IgG kappa myeloma antibodies are producing interference on IFE tests. We offer this assay at all of its central labs.
- Flow cytometry – a centralized approach is also being established for flow cytometry minimal residual disease (MRD) testing. Centralized interpretation will be undertaken by the team in Indianapolis.
- Plasma cell enrichment – bone marrow specimens can be received and enriched globally, from various labs, with the frozen aliquot plasma samples sent to a central lab, for interpretation of fluorescence in situ hybridization (FISH) testing.
Fighting Multiple Myeloma Requires Consistency and Reliability
Multiple myeloma is a dynamic and complex disease requiring a high level of consistency and reliability in testing and data interpretation. Our CLS are committed to providing sponsors an industry-leading, centralized multiple myeloma service offering and robust, well tested procedures.
Other Blog Posts in the Multiple Myeloma Series:
CRO Perspectives: Driving Innovation, Consistency and Reliability in Multiple Myeloma Clinical Trials This blog post provides an overview of the current landscape and challenges in multiple myeloma clinical trials. Read now.