By Turna Ray
The latest diagnostic in Abbott's portfolio to receive a thumbs up from the US Food and Drug Administration is a genetic test aimed at predicting the prognosis of acute myeloid leukemia patients.
The FDA this week granted 510(k) clearance to Abbott's Vysis EGR1 FISH Probe Kit, a fluorescence in situ hybridization test that detects a chromosomal deletion in bone marrow that has been associated with a poor prognosis for AML patients. The green light for the AML prognostic follows the approval in August of Abbott's Vysis ALK Break Apart FISH Probe test indicated to identify ALK-positive non-small cell lung cancer patients who may benefit from treatment with Pfizer’s NSCLC drug Xalkori.
"The Vysis EGR1 FISH Probe Kit is intended to detect deletion of the LSI EGR1 probe target on chromosome 5q in bone marrow specimens," the FDA-cleared label for the AML test states. According to the label, the genetic test should be used in concert with cytogenetics, other biomarkers, morphology, and other clinical information to inform physicians of their patients' prognosis at the time they are diagnosed with acute myeloid leukemia.
Abbott previously sold its LSI EGR1 assay as an analyte specific reagent. However, the FDA's 2007 ASR guidance states that sponsors are violating the Federal Food, Drug, and Cosmetics Act if they combine or promote the use of a single ASR with other ASRs, general purpose reagents, controls, or lab instruments and software.
An Abbott spokesperson told PGx Reporter that the company pursued 510(k) clearance for the LSI EGR1 FISH Probe Kit to stay in line with FDA regulations and provide physicians and patients with a well-validated clinical tool for AML prognosis. While many labs have used the Abbott ASR probe as the basis for laboratory-developed tests for this indication, Abbott's is the first kit to receive FDA clearance, according to the spokesperson.
The 510(k)-cleared test, which became available on the market as of Oct. 20, will be sold to labs that perform cytogenetics or FISH testing. Abbott didn't specify how much the test would cost. "The cost of the test will vary for individual laboratories based on negotiated contracts and volumes," the Abbott spokesperson said.
More than 12,000 people are diagnosed with AML each year, making it the most common type of leukemia to affect older adults. The disease causes rapid growth of abnormal white blood cells, which overcome healthy cells and impair the body's infection-fighting capabilities. The rapid progression of the disease results in most AML patients receiving aggressive chemotherapy treatment, and in some cases, stem cell transplantation of unhealthy bone marrow.
"At the time a patient is diagnosed with AML, the physician can perform an EGR1 FISH test to help identify what particular risk category the patient is in based on chromosomal status or changes," the Abbott spokesperson said. "Based on these categories and other factors, physicians are able to determine prognosis."
According to the latest guidelines from the National Comprehensive Cancer Network, cytogenetic analysis represents the "single most important prognostic factor for predicting remission rate, relapse, and survival" for AML patients. "The importance of obtaining adequate samples on marrow or peripheral blood at diagnosis to do full karyotyping as well as FISH probes for the most common abnormalities cannot be overemphasized," the NCCN 2011 guidelines state.
Prior studies have linked del(5q) abonormalities to unfavorable prognosis in AML patients. Abbott cited an Eastern Cooperative Oncology Group clinical trial, which found that FISH technology was useful in separating AML patients into risk categories based on chromosomal status or changes. Doctors were subsequently able to develop disease-management approaches for these different categories.
Separately, there is ongoing research to treat myelodysplastic syndromes based on cytogenetic and other risk factors. For example, Celgene markets lenalidomide, also called Revlimid, for patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with del(5q) cytogenetic abnormalities. The drug developer is continuing to study the drug in combination with other treatments in various MDS indications.
In a study presented at the American Society of Hematology's annual meeting last year, researchers reported that combining lenalidomide with intensive induction chemotherapy may yield promising response rates in AML patients with del(5q) chromosomal abnormalities. The study — which included 48 higher-risk patients with myelodysplastic syndromes or AML and del(5q) abnormalities — found that "intensive chemotherapy and lenalidomide can be combined … without unexpected additive myelosuppression or extra hematological DLT."
The trial, led by Lionel Ades of France's Hopital Avicenne and funded by several drug developers, including Celgene, found that the complete response rate among this cohort with "very poor cytogenetics" was 50 percent higher than reported generally when similar patients are treated with chemotherapy alone.
However, disease-free survival of patients remained short, "suggesting that induction or consolidation therapy should be improved," the researchers reported.
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