Palmetto GBA’s MolDX Announces Coverage of MRD Testing

In an important advance for precision medicine, the Medicare administrative contractor Palmetto GBA, through its Molecular Diagnostic Services Program (MolDX), has recently finalized a local coverage determination (LCD) for tests for minimal residual disease (MRD).¹ Following the release of a draft policy in September 2020, the final LCD in MRD testing was announced November 11.

The decision, which takes effect December 26, covers the Adaptive Biotechnologies Corporation’s clonoSEQ test to detect and monitor MRD for patients with B-cell acute lymphoblastic leukemia, multiple myeloma, and chronic lymphocytic leukemia. The LCD also creates a pathway for clonoSEQ’s use in other indications.²

The LCD also covers Natera, Inc’s Signatera MRD test for several indications involving patients with solid and hematopoietic cancers.³

In its notice, MolDX cited National Coverage Determination 90.2, which “allows contractors to cover next-generation sequencing tests as a diagnostic laboratory test for patients with cancer in specific circumstances.” MolDX outlined 10 specific conditions that must be met for MRD tests to receive coverage; the conditions include, but are not limited to, the following¹:

• The patient must have a personal history of cancer with the type and staging that matches the intended use of the MRD test.
• The use of the test must align with guidelines from the National Comprehensive Cancer Network “or other established guidelines as a condition that requires a definitive change in patient management.”
• The test is demonstrated to “identify molecular recurrence or progression” before evidence of progression is present and demonstrates “sensitivity and specificity of subsequent recurrence or progression” that is on par with radiological or other evidence of recurrence or progression.

As a comparatively new application of novel genomic technologies, MRD testing has been highly regarded for its sensitivity and specificity in allowing detection of extremely dilute tumor material or tracking the relative increase or decrease of tumor material being deposited in the blood.

Specifically, MRD testing can be leveraged to diagnose cancer progression, recurrence, or relapse before there is clinical, biological, or radiographical
evidence of progression, recurrence, or relapse as well as detect tumor response to therapy by measuring the proportional changes in the amount of available tumor DNA.

“Both above uses may enable physicians to better assign risk stratification, deploy alternate treatment strategies, or preclude the use of unnecessary adjuvant therapies,” the statement from MolDX said.¹

Several limitations have also been identified for MRD testing, including discordance of mutations between circulating tumor (ct) DNA and tissue, possibility of ctDNA enrichment with therapy resistance alterations, and inability to detect a second primary tumor.

“We are pleased that MolDX finalized the LCD for next-generation sequencing...tests for MRD, solidifying patient access to the critical results that our clonoSEQ assay provides across the continuum of care,” said Lance Baldo, MD, chief medical officer of Adaptive Biotechnologies. “This LCD
provides a pathway for the continued expansion of clonoSEQ into routine clinical care to benefit the more than 700,000 patients living with lymphoid malignancies in the United States. We look forward to our continued work with Medicare to help evolve coverage within this rapidly advancing field.”²

“Monitoring ctDNA kinetics with Signatera can identify treatment nonresponders earlier than imaging alone and independent of other biomarkers, including PD-L1 and tumor mutational burden...,” said Solomon Moshkevich, general manager of oncology for Natera. “We look forward to working with Medicare and with the oncology community to make personalized monitoring and MRD assessment accessible for cancer patients of all tumor types.”³

References

1. MolDX: minimal residual disease testing for cancer. CMS. Updated November 4, 2021. Accessed November 19, 2021. https://go.cms. gov/3cA4WaK
2. Adaptive Biotechnologies receives updated Medicare coverage for its
minimal residual disease (MRD) assay, clonoSEQ for blood cancer pa- tients. News release. Adaptive Biotechnologies Corporation. November 11, 2021. Accessed November 19, 2021. https://bit.ly/3HyoR82
3. Medicare publishes final local coverage determination for pan-cancer immunotherapy monitoring with Natera’s Signatera MRD test. News release. Natera Inc. November 11, 2021. Accessed November 19, 2021.
https://bit.ly/3qSqYxL

































minimal residual disease (MRD) assay, clonoSEQ for blood cancer pa- tients. News release. Adaptive
Biotechnologies Corporation. November 11, 2021. Accessed November 19, 2021. https://bit.ly/3HyoR82
3. Medicare publishes final local coverage determination for pan-cancer immunotherapy
monitoring with Natera’s Signatera MRD test. News release. Natera Inc. November 11, 2021. Accessed
November 19, 2021.
https://bit.ly/3qSqYxL