FDA approves NGS-based test to detect MRD

On 30 September 2018, the US Food and Drug Administration announced the approval of a new generation sequencing (NGS)-based test to assess minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) and multiple myeloma (MM). The clonoSEQ assay has been developed by Adaptive Biotechnologies and is the first NGS assay to gain approval for these conditions.

MRD is a measure of the remaining cancer cells in the bone marrow and has become the gold standard for assessing the efficacy of a treatment regimen. Whilst these cells do not cause disease symptoms, the percentage of cells remaining correlates with the length of remission and so is a useful parameter for both patients and doctors.

Methods to detect MRD can differ in sensitivity. Current flow cytometry and polymerase chain reaction (PCR)-based assays can only detect MRD down to 10^-4 or 10^-5, whereas NGS-based assays offer improved sensitivity and can detect as low as 10^-6 cells. Currently, testing will be carried out in-house at Adaptive Biotechnologies incorporation in Seattle.

The FDA approval followed a new process of premarket review - a regulatory pathway for novel devices, and is aimed at speeding up the process. Data to support the application was submitted from a retrospective analysis from three previous studies that included 273 ALL patients, 706 MM patients, and 323 MM patients. A correlation between MRD levels and event-free survival (EFS) was shown; patients with low MRD had prolonged EFS, whereas patients with a higher measured MRD had shorter EFS, and in MM patients there was a correlation with progression-free survival (PFS).