FDA Clears Genomic Bone Marrow Test for Low-Level Cancer

(Marco Verch, Flickr)

1 Oct. 2018. The Food and Drug Administration on Friday authorized for marketing in the U.S. a system for high-speed analysis of bone marrow samples to find low levels of residual cancer cells. The agency’s announcement cleared the ClonoSeq assay developed by Adaptive Biotechnologies in Seattle to test for minimal residual disease levels in people with B-cell acute lymphoblastic leukemia and multiple myeloma, two types of blood-related cancer.

B-cell acute lymphoblastic leukemia is a cancer of blood and bone marrow that progresses quickly, making an overabundance of immature lymphocytes, a type of white blood cell. It is also the most common type of cancer among children, although it can affect adults as well.  Multiple myeloma is a cancer of plasma cells, white blood cells helping fight infections by making antibodies that recognize invading pathogens. The disorder causes cancerous cells to accumulate in the bone marrow, crowding out healthy plasma cells. Instead of antibodies, the malfunctioning cancer cells produce abnormal myeloma proteins that cause kidney problems and other disorders.

Minimal residual disease measures the amount of cancer in the patient, in this case in bone marrow where the cancers occur. This low level of cancer can provide an indicator of a treatment’s effectiveness as well as a warning of the cancer’s relapse or recurrence. Minimal residual disease is also used as an endpoint or objective for cancer therapies in clinical trials. Because of the low levels of cancer in the blood, more highly-sensitive analytical methods are needed. Current testing methods, even those using genomic analysis, can detect residual cancer cells in concentrations as low as 1 in 100,000 cells.

The ClonoSeq assay adds next generation sequencing to the testing methods for minimal residual disease. Next generation sequencing harnesses advanced high-speed computing power to simultaneously analyze many genomic data streams, in this case to detect and measure malignant cancer cells remaining in DNA from a patient’s bone marrow. The test is able to identify concentrations of cancer as low as 1 in 1 million cells.

FDA cites results of clinical trials where negative ClonoSeq assay results show greater event-free survival of patients with B-cell acute lymphoblastic leukemia. Event-free survival is the amount of time a person with cancer lives without complications or other serious events. In another trial, negative results from the test were associated with greater progression-free and disease-free survival in patients with multiple myeloma. Progression-free survival is the length of time a person with cancer lives without further worsening of the disease. And disease-free survival is the amount of time someone with cancer lives without any signs of the disease recurring.

The agency authorized the clonoSeq assay under its de novo premarket review process for new types of low- to moderate-risk medical devices. However, FDA also established addition criteria it calls special controls spelling out expectations for accuracy, reliability, and effectiveness of tests measuring minimal residual disease in cancer patients. The de novo process combined with the special controls will provide FDA with a new regulatory classification for these kinds of devices, enabling further tests of this type to be reviewed under the agency’s 510(k) process, allowing new device developers to show evidence of equivalence with these criteria.

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