SIGNS OCCUR YEARS BEFORE AND MIGHTPOINT TO TARGETS FOR PREVENTION
Clues from an NCI-funded blood sample bank have led scientists to the startling revelation that almost all multiple myeloma patients show a distinct pattern of changes in blood many years before symptomatic disease begins.
In two studies published early this year in Blood, researchers report that the changes are linked to a well-known precursor stage of multiple myeloma called monoclonal gammopathy of undetermined significance (MGUS).
The longstanding question of whether myeloma is always preceded by this stage now appears to have an answer. "This shows once and for all that there is a premalignant stage that preceded virtually every multiple myeloma," the Mayo Clinic's Dr. S. Vincent Rajkumar, senior author of one of the papers, said in the NCI Cancer Bulletin.
In essence, he said, the early blood changes seen during MGUS appear linked to myeloma in much the same way that colon polyps precede and warn of possible colon cancer. This research therefore "gives us the impetus to find ways to identify the precursor stage and use the information to help patients," Dr. Rajkumar explained.
Multiple myeloma, which affects white blood cells known as plasma cells, has been particularly tough to study because of the paucity of blood samples taken from patients before they became sick. But since 1992 the NCI has been collecting and storing thousands of blood samples as part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
Overall, 71 of the more than 77,000 people enrolled in PLCO developed myeloma during the trial. Comparing early, pre-illness blood samples from those individuals to samples from PLCO participants without the disease, Dr. Rajkumar's team confirmed that in almost every case MGUS preceded myeloma—sometimes by as much as a decade before disease diagnosis.
These results were replicated in a second study, based on a similar analysis of stored blood samples from military personnel. In that study, 27 of 30 multiple myeloma cases were preceded, years before, by MGUS. "We came up with a very similar answer [as the PLCO study]," study co-lead author Dr. Michael Keuhl, of the NCI's Center for Cancer Research, told the Bulletin.
So what now? Because MGUS affects 3 percent of Americans over 50 but only rarely leads to myeloma, it would be both impractical and costly to treat MGUS-even if such a therapy existed. But the new findings should advance our understanding of the natural course of MGUS/myeloma, and perhaps spot markers that could someday identify individuals at risk for malignancy.
Already, a longitudinal study to examine issues like those is in development. The ultimate goal, the researchers say, is a kind of pre-emptive strike at MGUS that might eliminate the possibility of multiple myeloma before it starts.
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