Whole Genome Test for Blood Cancers Unveiled

The first whole-genome sequencing test for cancer to be approved for reimbursement by the Centers for Medicare & Medicaid Services is a novel test for two blood malignancies developed by a team at Washington University School of Medicine in St. Louis. The ChromoSeq test advances precision medicine approaches for treating blood cancers by identifying the full suite of genetic changes in a patient’s cancer cells, providing critical information that doctors can use to help determine the best treatment strategy for individual patients.

Since 2021, Washington University clinicians have frequently employed ChromoSeq to guide treatment decisions for patients at Siteman Cancer Center with acute myeloid leukemia (AML) or a group of blood malignancies known as myelodysplastic syndrome (MDS). Siteman works at Barnes-Jewish Hospital as well as Washington University. With Medicare clearance, physicians around the country who care for Medicare patients diagnosed with AML or MDS will be able to order the test through Washington University Pathology Services, and Medicare will reimburse the cost.

“This approval reflects the power and clinical validity of ChromoSeq to assess the full range of genetic mutations responsible for some of the most deadly blood cancers, which can help guide treatment decisions for individual patients,” said Richard Cote, MD, the Edward Mallinckrodt Professor and head of the Department of Pathology & Immunology, which runs the pathology service in collaboration with the clinical sequencing laboratory at WashU Medicine’s McDonnell Genome Institute. “Private insurance companies often follow Medicare’s lead in coverage decisions, so we expect that there will be demand for this test across the country. This approval stands as a testament to the vision of WashU physician-scientists Eric Duncavage, Dave Spencer, Molly Schroeder and their team, who spent years developing and validating this test.”

Costs have reduced considerably in recent years as genome sequencing technology has evolved, making Medicare reimbursement conceivable. The McDonnell Genome Institute, which specializes in genome sequencing and analysis, will conduct the tests. The Genome Institute scientists were the first in the world to demonstrate the efficacy of whole-genome sequencing in pinpointing genetic flaws responsible for cancer growth and progression.

The treatment for AML and MDS is determined by the severity of the malignancies in each patient. To put the cancer in remission, severe tumors require rigorous treatment with chemotherapy medications and, in some cases, a stem cell transplant, but less aggressive blood cancers can often be adequately treated with less intensive drug regimens. Treatment decisions are usually based on the genetic changes displayed by a patient’s malignancy. Standard tests employed in a patient’s diagnostic workup may only examine some of these changes and provide a limited perspective of the genetic abnormalities that may be causing a patient’s cancer to grow.

Genetic changes are currently assessed using a combination of three tests: cytogenetics, which reveals chromosomal rearrangements and abnormalities; fluorescence in-situ hybridization, which identifies chromosomal abnormalities as well as other mutations; and targeted sequencing of specific genes previously linked to AML and MDS.

In 2021, David H. Spencer, MD, PhD, an associate professor of medicine; Eric J. Duncavage, MD, a professor of pathology and immunology; Molly C. Schroeder, PhD, an assistant professor of pathology and immunology; Shelly O’Laughlin, director of clinical operations at the McDonnell Genome Institute; and Timothy J. Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Medicine published a landmark paper in The New England Journal of Medicine.

“All of the information that you can get from the three different tests that doctors now order as standard of care, we can get from ChromoSeq in one test,” said Meagan Jacoby, MD, PhD, an associate professor of medicine. “That can be important because sometimes the other tests don’t produce reliable results, and without that data, we have less confidence in our ability to assess a patient’s risk of aggressive disease. Knowing whether a patient is at low or high risk of aggressive disease is essential for us to know how to treat each patient most appropriately.”

Jacoby is leading two ongoing clinical trials to assess how ChromoSeq data compares to standard-of-care testing and how clinicians use ChromoSeq in real-world settings. Because ChromoSeq collects data from the entire genome, it can look for known mutations that are too infrequent to be detected by focused genetic sequencing studies. Preliminary data from two ongoing clinical trials, according to Jacoby, reveal that, when compared to standard tests, ChromoSeq can yield new information that could influence how particular patients are treated. The whole impact of ChromoSeq will not be known until the trials are finished.

ChromoSeq can also be swiftly updated as new evidence on how specific genetic changes relate to blood malignancies becomes available.

“If we want to look at additional genes or mutations, all we’d have to do is modify our data analysis slightly,” said Spencer, also the medical director of the clinical sequencing facility at the McDonnell Genome Institute. “Analysis of new regions would still need to be validated, but technical aspects of the assay in the lab would not need to be changed.”

The invention of ChromoSeq is the latest in a long line of remarkable genomic science achievements at WashU Medicine. Ley and colleagues at the McDonnell Genome Institute were the first in the world to employ whole-genome sequencing to identify the whole array of genetic alterations in a cancer patient’s tumor cells and trace the cancer’s hereditary roots in 2008. This pioneering discovery lay the framework for countless other studies using whole-genome sequencing in practically every type of cancer, as well as advanced precision medicine approaches to cancer treatment based on a patient’s tumor’s underlying genetics.

“Sequencing the first cancer genome was a phenomenal achievement that took over a year and cost over $1 million dollars,” said Duncavage, also chief of the molecular oncology section in the Department of Pathology & Immunology. “Now we’ve reached the point where we can sequence a cancer genome in a few days for a few thousand dollars, and Medicare will cover the cost as it does for other clinical tests.”

The researchers are now working on creating whole-genome sequencing techniques for additional types of cancer, beginning with acute lymphocytic leukemia and multiple myeloma.

“We chose those cancers because they involve the same kinds of patient samples — blood and bone marrow — so we can use the same laboratory procedures that we established for AML and MDS,” Spencer said. “With only slight modifications to this assay I can see a lot of potential for whole-genome sequencing to transform how we diagnose and treat other kinds of cancer.”

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