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Molecular Marker Testing Dialogue Continues at ASH

By Edward Li, PharmD, BCOP, Drugs and Biologics Editor

At the recent 52nd Annual Meeting of the American Society of Hematology (ASH), numerous scientific presentations discussed new information and discoveries revolving around genetic and other molecular markers. There is no doubt that the use of molecular markers to inform the diagnosis, prognosis, and treatment decisions of patients with cancer is an increasing focus. For example, a session focusing on chronic lymphocytic leukemia (CLL) reviewed established and emerging prognostic markers for this disease and discussed how this information can be used to inform treatment decisions. Additionally, a session entitled, "Genome-Wide Association Studies in Hematology," highlighted the need to conduct impactful research to identify additional clinically important molecular markers. The importance of identifying new targets for therapy was also emphasized in the "Best of ASH" wrap-up on the last day of the meeting.

Numerous posters presented at the meeting described research that investigated various gene mutations in acute myeloid leukemia. Some of this research explored whether these mutations can be useful in predicting patient outcomes, and whether they can be used to determine risk stratification. As new molecular markers in oncology are discovered, it will be interesting to see how they will become incorporated into clinical practice. In order for a molecular marker test to be clinically useful, the information obtained from performing the test will be used to inform diagnosis, prognosis, and treatment decisions to improve patient outcomes. Thus, clinicians must clinically evaluate the evidence behind the utilization of these tests to determine how they will use them in day-to-day practice. Furthermore, clinicians must be able to distinguish between molecular marker tests with practical significance versus tests that have insufficient data to recommend routine use.

Regulatory issues regarding the assays for detecting molecular markers must be addressed as well: how will these tests be regulated by the Food and Drug Administration (FDA)? Will they be developed as medical devices (and therefore subject to FDA approval), or will they be available as Laboratory Developed Tests (LDT)? LDTs are "diagnostic tests that are developed, validated and performed by individual laboratories," for the purpose of diagnosing rare diseases or conditions for a specific, local population of patients.¹ In the past, the FDA "has not actively regulated most LDTs," but they intend to increase their oversight of them because of concerns with increasing complexity and commercial interest.² Many tests to detect molecular markers in oncology are LDTs, so it is important to assess how these regulations will impact patient care.

Also, it is unknown how managed care organizations plan to evaluate the significance of molecular tests in oncology. They typically perform their own analyses for specific molecular tests (for example, the Blue Cross Blue Shield Technology Evaluation Center has researched and evaluated the use of KRAS mutational testing in colorectal cancer and gene profiling in breast cancer), and their determinations may possibly conflict with the thinking of health care providers.

As the breadth of information advances, so too does the need to provide authoritative guidance regarding proper tests and their corresponding utility from the clinical, scientific, and coverage policy standpoints. Ideally, future guidance regarding the utilization of molecular tests will be modeled after the current process for determining coverage of drugs and biologics. To discuss some of these issues noted above, NCCN plans to convene an Oncology Policy Summit on Molecular Testing in 2011. As with other NCCN Oncology Policy Summits, this will be a forum for key policy organizations, thought leaders, and other stakeholders to participate in discussions about how these new regulations will impact oncology care.

¹ Flannery E and Danzis S. FDA Plans to Regulate Laboratory Developed Tests as Devices. Journal of Medical Device Regulation. 2010;7(3):63-66.

² FDA/CDRH Public Meeting: Oversight of Laboratory Developed Tests (LDTs). Food and Drug Administration Web site. Available at:http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm212
830.htm#background. Accessed December 9, 2010.