There appears to be concordance among the clones and subclones detected by whole-exome sequencing on bone marrow and blood biopsies, Dr Nooka acknowledged.

“But at this point [in] time, these tests may be complementary to each other, rather than a replacement,” he said.

While clonoSEQ is approved for MRD detection in B-cell ALL and multiple myeloma, assays for myeloid malignancies are still needed.

“High-sensitivity measurement of residual disease in blood cancers that derive from cells of the lymphocyte lineage, like acute lymphocytic lymphoma, lymphoma, and myeloma is greatly aided by the ability to follow rearranged immune-receptor genetic sequences associated with the cancer clone,” Dr Hourigan told Cancer Therapy Advisor. “Blood cancers derived from other cell types, such as myelodysplastic syndrome and acute myeloid leukemia, are more challenging to track due to the lack of such a clone-specific rearranged genetic sequence,although this is an intense area of research, both in my laboratory at the NHLBI and elsewhere.”

Dr Hourigan and colleagues have developed a high-sensitivity RNA NGS assay for AML MRD.4

Dr Ravandi and colleagues are also looking for NGS markers of MRD in AML. They plan to publish early findings from that effort, but Dr Ravandi cautioned that such an assay “is still a long way from becoming a reality” in routine clinical care.

Such assays will eventually help improve patient outcomes in several malignancies, Dr Ravandi prophesied — including,he hopes, in AML.

But more AML drug development is needed, as well, Dr Ravandi added. “To recognize MRD and see it’s associated with worse outcomes is one thing, but unless you can do something about it, its full potential benefit for the patient is unclear.”

Disclosures: Dr Nooka received an honorarium from Adaptive Biotechnologies in 2016. Dr Ravandi and Dr Hourigan indicated that they have no relevant disclosures.


  1. Adaptive Biotechnologies. Adaptive Biotechnologies announces Medicare coverage of the clonoSEQ® Assay for MRD testing in patients with multiple myeloma and acute lymphoblastic leukemia at multiple timepoints throughout treatment and remission. Published January 17, 2019. Accessed February 10, 2019.
  2. United States Centers for Medicare & Medicaid Services. MolDX: Clonoseq® Assay for assessment of minimal residual disease (MRD) in patients with specific lymphoid malignancies (A56270). Published January 17, 2019. Updated January 31, 2019. Accessed February 10, 2019.
  3. US Food and Drug Administration. FDA authorizes first next generation sequencing-based test to detect very low levels of remaining cancer cells in patients with acute lymphoblastic leukemia or multiple myeloma [press release]. Published September 28, 2018. Accessed February 5, 2019.
  4. Dillon LW, Hayati S, Roloff GW, et al. Targeted RNA-sequencing for the quantification of measurable residual disease in acute myeloid leukemia. Haematologica. 2019;104:297-304.