New rapid assay developed to support medicine trial for blood cancers

The Molecular Characterization Laboratory at Frederick National Laboratory for Cancer Research (FNL) and collaborators at Fred Hutchinson Cancer Center(Fred Hutch)  developed and validated a new, precise assay for detecting cancer-driving mutations in critically ill people with diagnoses of blood cancers.  

The performance data from the assay, NMAv2, appear in the Journal of Molecular Diagnostics. FNL and Fred Hutch scientists designed NMAv2 for the National Cancer Institute’s myeloMATCH precision medicine trials, where they’re using it to identify mutations in the DNA and RNA of people newly diagnosed with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). 

The goal is to determine whether patients’ blood cancers harbor molecular alterations that make them vulnerable to the drugs being tested in myeloMATCH—and to do so quickly and accurately for each patient. Many AML patients require immediate treatment, as their cancers are so aggressive they prove fatal in as little as two months of diagnosis if left untreated. 

NMAv2 tests for all mutations and gene fusions that classify the hematopoietic disease and deliver results with clinical accuracy in less than 48 hours. 

Existing methods have longer turnaround times—averaging two to three weeks—and results are not as comprehensive, said Shahanawaz Jiwani, M.D., Ph.D., director of pathology at the FNL Molecular Characterization Laboratory (MoCha) and chair of the myeloMATCH laboratory effort. 

“Before this, no one was able to sequence a [leukemia] genome [panel] in a day, even with other high-powered assays,” he said. 

In validation tests conducted at the MoCha and Fred Hutch sequencing laboratories, NMAv2 identified the presence of target mutations with a 0% false-positive rate and pinpointed individual mutations with 99% accuracy. The teams reproduced its results with greater than 99% consistency. 

Consequently, Jiwani said myeloMATCH doctors and clinicians can trust that the assay’s results are correct, regardless of which of the two laboratories screens a patient’s samples. 

“This technology plays a pivotal role in getting clinicians the information they need to treat these patients appropriately and in a time frame necessary to treat these patients accurately,” he said.  

Door-to-door in three days 

With NMAv2, myeloMATCH clinicians can receive a patient’s results within 72 hours of sending the biopsies for testing. 

That includes the time needed to ship patients’ samples overnight from the treating hospital to either MoCha, which handles sequencing on weekdays, or Fred Hutch, which handles the sequencing on weekends, Jiwani said.  

For doctors, that means there’s little delay before they can ascertain how best to treat their patient. For patients, there’s no stressful, weeks-long wait to receive potentially lifesaving cancer treatment.  

Once a sample arrives at the sequencing laboratories, a technician extracts the DNA and RNA and preps it for NMAv2. MoCha staff runs the samples using next-generation sequencing technology and a pathologist reviews the results the following day before Jiwani releases them to the clinicians at the hospital. 

“Then [they] can treat the patients in the best scientifically possible way,” Jiwani said.  

myleoMATCH established for patients with blood cancers

The myeloMATCH trials are led by the Southwest Oncology Group and are part of the Molecular Analysis for Therapy Choice (MATCH) family of precision medicine trials launched in 2015 by NCI and the ECOG-ACRIN cancer research group. 

The original NCI-MATCH trial sought to determine whether drugs approved for treating one type of cancer with specific mutations could also treat other cancers with the same mutations in patients who had already received standard therapies for their cancers. Patients’ cancer biopsies underwent next-generation sequencing to identify potential  mutations and by this knowledge assign the patient to any appropriate targeted therapy. 

myeloMATCH focuses on treating new, previously untreated cases of AML and MDS with targeted drugs and combination therapies. Patients whose cancers harbor candidate mutations are assigned to the corresponding treatment. 

Those whose cancers don’t have any actionablemutations are instead given a standard   antineoplastic  but they may be eligible to participate in later phases of myeloMATCH.  

So far, approximately 600 people have been enrolled and had their biopsies sequenced. That’s about 3% of all the people in the U.S. who will be diagnosed with AML this year, an uncommonly and impressively large sample size for a clinical trial, Jiwani said.