Whole Genome Sequencing for AML/MDS Risk Stratification

Meagan Jacoby, MD, PhD

Two novel clinical trials for patients diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) are open and enrolling patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis.

The clinical trials are utilizing a breakthrough whole-genome sequencing test, ChromoSeq, developed by researchers and cancer specialists at WashU and recently approved for reimbursement by the Centers for Medicare & Medicaid Services.

“One clinical trial is enrolling AML and MDS patients admitted to our inpatient service, and the second trial is for MDS patients who are being seen in outpatient settings,” says medical oncologist Meagan Jacoby, MD, PhD, principal investigator of the 2 studies.

The trials are designed to better pinpoint genetic mutations in the two blood cancers so that patients can be risk-stratified to optimal treatments. In addition, researchers are tracking how ChromoSeq is used by physicians to guide and/or change initial treatment recommendations.

“We published our initial findings on the ChromoSeq whole-genome sequencing test in the New England Journal of Medicine in 2021 showing that it can be more accurate than other tests currently in use to identify specific genetic mutations,” says David Spencer, MD, PhD, medical director of the Clinical Sequencing Facility in the McDonnell Genome Institute at WashU and the physician-scientist who led the team that developed and validated the ChromoSeq test. “As whole-genome sequencing gets even faster and less expensive, we believe it will become the routine way we test for mutations in cancer patients.”

Optimal treatment for both AML and MDS is guided by the diseases’ genetic mutations and overall aggressiveness. Currently, multiple tests are used to obtain this information and some of these can miss important mutations. In contrast, ChromoSeq identifies the full range of genetic mutations in cancer cells using a single test and, in some cases, can offer a more precise diagnosis of a patient’s cancer.

“All risk stratification tools require genetics to guide therapy,” notes Dr Jacoby. “The current tests give us multiple separate results that provide this information. With whole-genome sequencing, we get a complete look at the genetic components of a patient’s cancer with one approach. In some cases, we learn critical new information that can be difficult to find with conventional tests.”

Says Dr Spencer, “The third AML patient we sequenced with ChromoSeq had a rare mutation that is found in only about one percent of patients and is challenging to detect with conventional tests. The mutation is associated with poor response to chemotherapy and is one example of how ChromoSeq can benefit patients with this cancer.”

In a more recent example, Dr Jacoby says, a patient initially identified to be at intermediate risk for relapse was later determined to be at higher risk after reviewing the results of their ChromoSeq test. The finding altered treatment recommendations.

Consider ChromoSeq Testing for Your Patients

ChromoSeq research has been so promising with AML and MDS that Dr. Spencer and others are expanding research into its use with other cancers, including multiple myeloma and acute lymphoblastic leukemia (ALL), the most common form of childhood leukemia.

Currently, ChromoSeq testing is available only through Washington University Pathology Services for AML and MDS patients. The test is most beneficial when used to guide therapy at the time of diagnosis; however, it also can be used to determine next steps after relapse.

Physicians interested in obtaining a whole-genome sequencing test for their AML and MDS patients can submit samples of bone marrow or peripheral blood and fill out an order form at https://pathologyservices.wustl.edu/services-tests/chromoseq/. Physicians will then receive a comprehensive report noting the percentage and type of gene mutations as well as risk stratification information.

“We give physicians the precise information they need to optimize treatment recommendations,” stresses Dr Spencer. “This can make a difference in patient care. Ultimately, we think it could improve outcomes. I think ChromoSeq is the latest example of precision medicine applications that are becoming a routine part of cancer care.”

For patient criteria information about open ChromoSeq clinical trials, contact our Patient Care Coordination Center at 314-747-3046 or siteman.wustl.edu/contact.

To view the full list of active clinical trials at Siteman, visit siteman.wustl.edu/clinical-trials.