FDA Approves Next-Generation Sequencing Test For MRD Detection

The US Food and Drug Administration (FDA) has approved a next-generation sequencing assay, clonoSEQ, to detect minimal residual disease (MRD) in patients with multiple myeloma or acute lymphoblastic leukemia.

MRD is a measure of residual cancer cells or tumor burden following treatment. It is indicative of treatment efficacy and patient prognosis and will help clinicians manage patient care, according to FDA Commissioner Scott Gottlieb, MD.

“I’d certainly echo [Gottlieb] and I would also point out that approval of this reproducible method helps standardize testing so that doctors and patients can compare ‘apples to apples’ across centers and treatments,” said Christopher S. Hourigan, PhD, ACP, FRCP, Laboratory of Myeloid Malignancies, at the National Heart, Lung, and Blood Institute in Bethesda, Maryland.

The FDA reviewed analysis of data from three retrospective clinical trials representing 273 patients with acute lymphoblastic leukemia and a total of 1,029 with multiple myeloma.

The approval was “an unprecedented move by the FDA,” said Ajay K. Nooka, MD, MPH, FACP, of the Emory University Winship Cancer Institute in Atlanta. Nooka predicted the clonoSEQ assay will be used for clinical trials in which MRD is a surrogate endpoint for survival and clinical decision making as well.

The clonoSEQ assay allows detection of myeloma cells “at a much deeper level” and MRD negativity is associated with better progression free survival.

“Historically, the goal of treatment for multiple myeloma is to attain the deepest response possible with the available therapies for that period, and the lowest tumor burden has always correlated with the best disease-free outcomes,” Nooka said.

In recent years, newer combination regimens involving immunomodulatory agents like lenalidomide and pomalidomide, proteasome inhibitors like bortezomib, carfilzomib and ixazomib, and monoclonal antibodies like elotuzumab, and daratumumab, have led to improved, deeper responses.

That necessitated a more sensitive measure of the depth of response.

clonoSEQ appears to meet that need. It can detect one myeloma cell in a million cells, Nooka noted.

An MRD-negative status was associated with significantly better progression free survival and overall survival, according to Nooka. 

“Patients have a right to the best available estimate of their residual cancer burden after treatment, so that they can make informed decisions about subsequent therapy, Hourigan said. “While it may make intuitive sense that deeper responses to therapy would be associated with prolonged survival, this needs to be proven for each particular treatment approach.”

It is also important we consider test results in terms of patients’ individual goals and priorities, he said.

“At the end of the day we as oncologists treat the patient not the number, and we’ll need to balance the risks of toxicity and cost of additional treatment for each patient with prospect of benefit in terms of prolonged survival and improved quality of life,” Hourigan said. “Having an accurate ‘handle’ on cancer remission status at clinically important time points will allow those conversations between patients and their oncologists to be more meaningful, specific and evidence-based.”