College of American Pathologists
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September 2011

News read or heard lately

New approvals of drug-diagnostic pairs

The Food and Drug Administration in August approved two new test-drug combinations.

Abbott received approval for a molecular test for rearrangements of the anaplastic lymphoma kinase, or ALK, gene in non-small-cell lung cancer. The new Vysis ALK Break Apart FISH Probe test identifies ALK-positive NSCLC patients for Pfizer’s approved NSCLC therapy, Xalkori (crizotinib), an oral first-in-class ALK inhibitor.

Roche won approval for its Cobas 4800 BRAF V600 Mutation Test for use with the approved drug Zelboraf (vemurafenib) for the treatment of BRAF V600E mutation-positive unresectable or metastatic melanoma. Roche and Plexxikon, a member of the Daiichi Sankyo Group, co-developed Zelboraf.

The Vysis ALK FISH test uses Abbott’s FISH technology to detect rearrangements of the ALK gene on the 2p23 chromosome. The test is designed to identify the three to five percent of NSCLC patients who would be candidates for Xalkori.

Xalkori was studied in 255 patients with locally advanced or metastatic ALK-positive NSCLC across two multicenter, single-arm studies. Zelboraf’s approval is based on the results of two clinical studies, BRIM 3 and BRIM 2. BRIM 3 is a multicenter phase three study that compared Zelboraf to dacarbazine chemotherapy in 675 patients with previously untreated BRAF V600E mutation-positive unresectable or metastatic melanoma. BRIM 2 is a multicenter, single-arm phase two study of 132 patients with previously treated V600E mutation-positive unresectable or metastatic melanoma.

Bringing costs under control

Without an answer to the question of what medical care is worthwhile and what is wasteful, there is no hope that an appropriate policy process for reining in health care costs will be identified, said Robert H. Brook, MD, ScD, in the Aug. 10 issue of the Journal of the American Medical Association.

The answer to the question must come from physicians, he writes in his editorial, “The role of physicians in controlling medical care costs and reducing waste” (306:650–651).

Dr. Brook, of RAND Corp. and the University of California Los Angeles David Geffen School of Medicine, says physicians face three scenarios in controlling costs. The first is to do nothing. “But sooner or later, with or without the help of physicians, the cost crisis will have to be confronted,” he writes, and the solution may not be what physicians or their patients want.

In the second scenario, health care is rationed. And in the third, physicians take the lead in identifying and eliminating waste. How? By assigning all services to one of four types of care: inappropriate, equivocal, appropriate, or necessary.

“With inappropriate care, the potential health benefit to the patient is less than the potential harm caused by the procedure, device, or drug. With equivocal care, potential harm and benefit are about equal. With appropriate care, potential benefit to the patient exceeds potential harm. Necessary care is appropriate, represents the only viable option, and produces a large health benefit,” Dr. Brook writes.

Sequencer, HLA typing kits submitted to FDA

Life Technologies has submitted its 3500 Dx Genetic Analyzer and SeCore HLA Sequencing System to the Food and Drug Administration for 510(k) clearance.

If cleared, the Applied Biosystems 3500 Dx/3500xL Dx Genetic Analyzer CS2 and the Invitrogen SeCore HLA Sequencing System would be the first 510(k)-cleared sequence-based test for HLA typing in the United States.

The 3500 Dx instrument has a consumables design that incorporates the ability to track information with radiofrequency identification tags, new optical and thermal sub-systems, and redesigned data collection and analysis software.

“A 510(k)-cleared sequencing instrument would pave the way toward establishing genomic medicine as a mainstay of the clinical lab,” said Todd Laird, VP and general manager of the company’s Fragment and Sequence Genomics Division, in a statement. “The 3500 Dx was designed to meet the hospital lab’s needs for reliability and user-friendly operation.”

It is also expected that clearance would facilitate additional assay development for the 3500 Dx. In May, Life Technologies announced a partnership with Gen-Probe to develop diagnostic assays for the platform, and it continues to seek additional partners to develop the assay menu.

Tissue of Origin Test works with body fluid specimens

The results of a study published online in Cancer Cytopathology (doi: 10.1002/cncy.20167) demonstrate that specimens prepared from cytologic body fluids yield adequate diagnostic material for the Pathwork Tissue of Origin Test and can be used in the workup of patients with unknown primary tumors.

“The ability to use body fluids—often the first or only specimen received for clinical evaluation in some cancer cases—in identifying the primary tumor site may be valuable in selecting appropriate therapies for these patients,” said Federico A. Monzon, MD, principal investigator and pathologist, The Methodist Hospital, Houston.

In the study, body fluid specimens prepared in standard formalin-fixed, paraffin-embedded format were generated according to routine protocols. The investigators found that 17 of 27 metastasis-positive fluid specimens yielded sufficient RNA for the Tissue of Origin Test. Of these samples, 94 percent (16 of 17) were in agreement with the available diagnosis, consistent with results reported for the Tissue of Origin Test in previous validation studies (J Mol Diagn. 2011;13:48–56).

A novel pathogenic ehrlichia agent

A new ehrlichia species has been identified in blood from four patients living in Wisconsin or Minnesota, by using molecular, culture, and serologic methods.

A study by Bobbi S. Pritt, MD, MSc, director of clinical virology and parasitology in the Division of Clinical Microbiology at Rochester’s Mayo Clinic, et al., in the Aug. 4 issue of the New England Journal of Medicine (365:422–429) reported that genetic analyses revealed that the new species, referred to as ehrlichia species Wisconsin, is closely related to E. muris. “Physicians need to be aware of this newly discovered close relative of E. muris to ensure appropriate testing, treatment, and regional surveillance,” the authors write.

Only Ehrlichia chaffeensis and E. ewingii have been thought to cause ehrlichiosis in humans in the United States. Anaplasma phagocytophilum is closely related to the ehrlichiae.

The four patients, ages 23 to 51, had an onset of illness between June 8 and Oct. 27, 2009. Laboratory findings included lymphopenia (in all four patients), thrombocytopenia (in three), elevated hepatic aminotransferase levels (in one of the three patients tested), and mildly elevated alkaline phosphatase levels (in one of the two patients tested). All four patients were treated with doxycycline and recovered.

“Commercial tests for ehrlichiosis may fail to provide an accurate identification of this organism,” the authors write. “The considerable serologic cross-reactivity of the Wisconsin isolate with E. chaffeensis could confound diagnostic and epidemiologic studies and may explain the recent increase in the numbers of cases attributed to E. chaffeensis infection in Wisconsin and Minnesota on the basis of serologic testing only. In addition, PCR assays for E. chaffeensis and E. ewingii may not detect ehrlichia species Wisconsin because of lack of primer and probe homology.” An ehrlichia-anaplasma real-time groEL PCR assay was used in the investigation.

Morulae are detected infrequently in blood from patients infected with ehrlichia species, the authors say, and were not found in blood from the four patients.

CLL prognosis test cleared

Abbott has received 510(k) clearance from the Food and Drug Administration for a new test to aid in determining the prognosis of patients with chronic lymphocytic leukemia. The test detects genetic abnormalities in lymphocytes.

The Vysis CLL FISH Probe Kit includes a panel of five individual FISH probes intended to detect deletion of the LSI TP53, LSI ATM, and LSI D13S319 probe targets and gain of the D12Z3 sequence in peripheral blood specimens from untreated patients with B-cell chronic lymphocytic leukemia. The assay may be used to dichotomize CLL (the 13q-, +12, or normal genotype group versus the 11q- or 17p- group) and may be used as an aid in determining disease prognosis in combination with additional biomarkers, morphology, and other clinical information. The kit is not intended for use in selecting therapy or in monitoring residual disease.

Siemens, JEOL to co-develop advanced chemistry platforms

Siemens Healthcare Diagnostics and JEOL have signed a strategic partnership to design, manufacture, and distribute new advanced clinical chemistry platforms. The 10-year agreement also extends an existing Siemens-JEOL relationship targeted at enhancing current systems within Siemens’ clinical chemistry portfolio.