Researchers have identified a small subset of genes whose activity could predict high-risk cases of multiple myeloma and potentially guide therapy decisions in the future. They presented their data recently at the American Association for Cancer Research's second International Conference on Molecular Diagnostics in Cancer Therapeutic Development. NCI provided partial funding for the study.
The investigators, from the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences, followed 532 multiple myeloma patients for 7 years after a blood stem cell transplant to create a genetic profile to chart the severity of the disease. The team determined that the activity of as few as 17 genes could mean the difference between high or low risk for a poor prognosis. About 30 percent of the genes that predict high risk are found on chromosome 1.
In addition, around 13 percent of all the patients they studied exhibited a genetic pattern that fit into the high-risk category, a frequency that rose to 76 percent among relapsed patients. An increase in the gene-expression risk score among relapsed patients provides evidence that there are likely to be small subsets of high-risk cells even in patients with low-risk disease, and that current therapeutics are suboptimal in that they kill off the low-risk cells, leaving behind cells that exhibit a high-risk genetic profile. "Gene expression profiles have now provided us with signposts that help us risk-stratify patients and tailor therapies accordingly," said lead researcher Dr. John D. Shaughnessy, Jr.
Bortezomib Multiple Myeloma Trial Halted after Analysis Shows Significant Survival Improvements
A phase III trial testing bortezomib (Velcade) plus the combination of two chemotherapy drugs for the first-line treatment of patients with newly diagnosed multiple myeloma has been stopped early based on recommendations of the trial's independent data monitoring committee (IDMC) so patients in the control arm can be switched over to the bortezomib treatment arm.
Millenium Pharmaceuticals, which manufactures bortezomib, announced last week that the IDMC halted the 682-patient trial, dubbed VISTA, after a planned interim analysis showed that the combination of bortezomib with melphalan and prednisone demonstrated a highly statistically significant improvement in overall survival and progression-free survival, as well as time-to-disease progression and complete remission rate compared with melphalan and prednisone alone.
"These results position [bortezomib]-based therapy as a new standard of care for newly diagnosed multiple myeloma patients," Dr. Paul Richardson, clinical director of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute and one of the trial's lead investigators, said in a statement.
During a conference call with investors and media, Millenium representatives said data from the analysis will be presented in December at the American Society of Hematology annual meeting. Dr. Nancy Simonian, Millenium chief medical officer, did say, however, that the results were consistent with those from a similar phase II trial presented in June at the International Myeloma Workshop in Greece, which showed a 43-percent complete response rate and a 3-year survival rate of 85 percent.
New FOBT Promising for Detection of Colon Cancer
In a large prospective study performed by investigators from three Northern California Kaiser Permanente medical centers, a type of fecal occult blood test (FOBT) called a fecal immunochemical test (FIT) showed high sensitivity and specificity for detecting left-sided colorectal cancer. The results were published in the September 25 Journal of the National Cancer Institute.
The investigators enrolled 7,394 eligible Kaiser Foundation Health Plan members aged 50 or older without a personal or family history of colon cancer into the study. All participants collected stool samples for use on three test cards, and the samples on each test card were used for three tests: a sensitive unrehydrated guaiac test (GT, a more sensitive version of the current standard FOBT), the FIT, and a combination of those two tests. Out of all participants, 5,841 prepared cards correctly and had at least 1 usable test result. Of these, 11 percent had at least 1 positive result.
Investigators recommended that all participants testing positive on the FIT or combination tests undergo colonoscopy, and all participants testing negative undergo sigmoidoscopy. Because most participants tested negative and underwent sigmoidoscopy, which can only visualize the left colon, only detection of left-sided colorectal cancer could be compared between tests. All participants were followed for 2 years, until diagnosis of a colorectal neoplasm, or until death, whichever came first.
The FIT had an 81.8 percent sensitivity for detecting colorectal carcinoma, and a 29.5 percent sensitivity for detecting advanced colorectal adenomas (noncancerous tumors). Specificity was 96.9 percent for carcinomas and 97.3 percent for adenomas, which increased to 98.1 percent and 98.4 percent in the combination test.
Although the investigators did not directly compare the FIT test with the current standard FOBT test, other recent comparisons have shown its superiority, they explain. "The FIT has high sensitivity and specificity for detecting left-sided colorectal cancer," they conclude, "and it may be a useful replacement for the [current standard test]."