More Details Presented on Melanoma Diagnostic Test

Much of the news at the Society for Melanoma Research, 2014 International Congress, involves breakthrough therapies for treating metastatic melanoma in its later stages. But the year has brought developments in diagnostics, too. Tools to determine which patients need aggressive treatment and which ones do not are becoming important. As awareness of melanoma grows, more patients arrive at doctors’ offices with suspicious skin marks at earlier stages.

Data on a melanoma diagnostic gene signature, marketed by Myriad Genetics Inc, as myPath, are being presented at SMR in posters.^1,2 Both data sets are successors to the 2013 results from Loren Clarke, MD, vice president of medical affairs at Myriad, and co-presenters, which described the development of myPath at the SMR Congress in Philadelphia.³ Last year’s poster outlined the process researchers followed when they began with 79 potential biomarkers, eventually culling them down to 23 that provided the greatest level of reliability in determining the difference between lesions that are malignant melanoma and benign nevi, or simple birthmarks.³

The myPath test produces a measurement, known as the melanoma diagnostic score or MDS. An MDS < 0 indicates a benign result, while an MDS ≥ 0 indicates the presence of melanoma. Data first presented in May at the American Society of Clinical Oncology, and shared at the 2014 Congress in Zurich, detailed clinical validity results. In another poster listing Clarke as the lead author, Myriad reports that the MDS can distinguish benign nevi from malignant melanoma with a sensitivity of 90% and a specificity of 91%.¹

New results presented in Zurich, “Analytical Validation of a Melanoma Diagnostic Gene Signature,” with M. Bryan Warf, PhD, as the lead author, offers an overview of the scientific process behind myPath. It details the steps to ensure its reliability, both as it was being developed and as an ongoing enterprise.² Key areas include:

Melanin inhibition. Tests were conducted to ensure that the MDS could be reproduced even if melanin contaminated the RNA extraction. This is important, because it ensures that the MDS is reliable and reproducible even in highly pigmented tissue samples.²

RNA yield and stability. Tissue samples from a 544-member cohort (272 benign, 272 with melanoma) were stored over 6-week period, with both RNA tests and MDS scores repeated at intervals to ensure that (1) the samples would continue to produce sufficient RNA for testing and (2) that the MDS produces on each sample at the intervals would hold up over the 6-week period. According to the results, the MDS was within 1 standard deviation for all samples.²

Dynamic range and precision. Researchers tested 4 RNA samples over a range of dilution points, and precision of the signature—and each measurement within it–was tested by running 30 samples in triplicate. Results produced found the signature and its individual measures were highly precise and reproducible over an extremely wide dynamic range.²

The results presented at SMR come on the heels of clinical utility findings released November 7, 2014, in Chicago, lllinois, at the 2014 meeting of the 2014 American Society of Dermatopathology (ASDP). At that meeting, Myriad reported that in a prospective study of 218 patients, use of the test produced 43% in indeterminate diagnoses and a 49% change in physicians’ treatment recommendations for patients.⁴ Since 2011, evidence of clinical utility has been increasingly important to payers when deciding whether to cover a diagnostic test, because insurers want to know that it affects treatment decisions.

Myriad spokesman Ron Rogers said that the new results would be of greatest interest to the scientific community. However, issues of test reliability, and practical issues such as the ability of tissue to be tested after being shipped some distance are of importance to payers as well. Issues of reliability in diagnostic testing are 1 reason the US Food and Drug Administration moved to provide greater oversight of the testing industry earlier this year.⁵

References

1. Clarke LE, Warf MB, Flake DD, et al. Clinical valiation of gene expression signature that differentiates benign nevi from malignant melanoma. Poster presentation at Society of Melanoma Research, 2014 International Congress, November 13-16, 2014, Zurich, Switzerland.

2. Warf MB, Flake DD, Adams D, et al. Analytical validation of a melanoma diagnostic gene signature. Poster presentation at Society of Melanoma Research, 2014 International Congress, November 13-16, 2014, Zurich, Switzerland.

3. Clarke LE, et al. Development of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. Poster presentation at Society for Melanoma Research International Congress, November 17-19, 2013, Philadelphia, Pennsylvania.

4. Myriad myPath Melanoma improves diagnosis and treatment plans: new prospective clinical utility data presented at the ASDP annual meeting [press release]. Salt Lake City, UT: GlobeNewswire; November 7, 2014. http://www.myriad.com/investors/press-release-detail/?newsItemId=881448.

5. FDA takes steps to ensure reliability of certain diagnostic tests [press release]. Silver Spring, MD: FDA Newsroom; July 31, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm407321.htm.