||Myeloma Prognostic Risk Signature (MyPRS)
||November 13, 2017
||November 13, 2017
Multiple myeloma (MM) is a malignant and often incurable hematological cancer, characterized by the abnormal and uncontrolled proliferation of plasma cells in bone marrow, leading to impaired hematopoiesis and production of monoclonal immunoglobulin (Ig). The disease is responsible for about 1% of all cancers worldwide and 10 to 15% of all hematological cancers. MM usually affects older adults (median age of onset is 71 and 74 years for men and women, respectively).
Clinical features of MM include anemia (73%), bone pain (58%), fatigue (32%), and unusual weight loss (25%). Diagnostic laboratory and clinical assessments include hypercalcemia, kidney dysfunction, anemia, and bone lesions.
The Myeloma Prognostic Risk Signature (MyPRS®) (Signal Genetics™) has been developed to estimate the underlying activity of disease progression, in patients diagnosed with active MM. The test may be used as a potentially useful risk stratification tool to predict treatment response to chemotherapy, predict risk of survival and relapse, and tailor therapy selection. Specifically, MyPRS may identify a high-risk patient group for disease progression based on the expression levels of 70 selected genes measured at baseline. It may be helpful to stratify patients into high-, high risk-borderline, low-risk borderline, and low-risk categories to optimize individual treatment.
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
|Policy Position Coverage is subject to the specific terms of the member’s benefit plan.|
MyPRS is considered experimental/investigational and therefore non-covered.
- Experimental/investigational molecular and genomic (MolGen) tests refer to assays involving chromosomes, DNA, RNA, or gene products that have insufficient data to determine the net health impact, which typically means there is insufficient data to support that a test accurately assesses the outcome of interest (analytical and clinical validity), significantly improves health outcomes (clinical utility), and/or performs better than an existing standard of care medical management option. Such tests are also not generally accepted as standard of care in the evaluation or management of a particular condition.
- In the case of MolGen testing, FDA clearance is not a reliable standard given the number of laboratory developed tests that currently fall outside of FDA oversight and FDA clearance often does not assess clinical utility.
|Professional Statements and Societal Positions|
Guidelines and Evidence
The National Comprehensive Cancer Network (NCCN, 2017) Clinical Practice Guidelines stated the following regarding gene expression profiling (GEP):
- “GEP is a powerful and fast tool with the potential to provide additional prognostic value to further refine risk stratification, helps therapeutic decisions, and inform novel drug design and development.”
- “The NCCN Panel unanimously agreed that although GEP is not currently routinely used in clinical practice during diagnostic workup, GEP is a useful tool and may be helpful in selected patients to estimate the aggressiveness of the disease and individualize treatment.”
- The NCCN Panel does not make any explicit recommendations for its use in its diagnostic and treatment pathways for cases of MM.
There is insufficient evidence in the peer-reviewed literature to draw definitive conclusions regarding the analytical validity, clinical validity, and clinical utility of the MyPRS test to accurately provide prognostic risk stratification among patients who are newly diagnosed with MM or who have relapsed following treatment.
- The evidence base mostly consists of retrospective studies evaluating small numbers of patients that evaluated the strength of the association between the MyPRS score with various survival measures; including post relapse survival, overall survival, and progression-free survival. Although the available studies reported significant associations between MyPRS and survival measures (patients with high MyPRS scores may be at increased risk of relapse and death), with study authors concluding that MyPRS has value as a risk stratification tool, the quality of the overall evidence is low given the retrospective study designs across the evidence base, and the lack of reported accuracy measures, including sensitivity, specificity, PPV, NPV, and clinical utility values. Furthermore, there is little to no evidence regarding the comparative accuracy of MyPRS with FISH testing or MyPRS with karyotyping. It is unknown if MyPRS can be an adequate substitute for FISH testing in patients with MM as part of the routine workup of the disease.
- Future prospective studies, allocating patients to therapies determined to be most effective based on MyPRS score, with adequate sample sizes, using gold standard diagnostic and/or prognostic measures, are necessary to elucidate its role as an adjunct to existing risk stratification measures or as a stand-alone test. Well-designed clinical utility studies are also needed to assess whether the MyPRS test leads to improved therapeutic clinical decision-making and improved patient outcomes.
|Place of Service: Inpatient/Outpatient|
Experimental/Investigational (E/I) services are not covered regardless of place of service.
MyPRS is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.
|The policy position applies to all commercial lines of business|
Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.
Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.
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