Fifty years after the US Air Force began spraying Agent Orange in Vietnam, new research shows that veterans exposed to the herbicide are more than twice as likely to develop monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma.
A team of researchers led by Ola Landgren, Chief of Memorial Sloan Kettering’s Myeloma Service, analyzed serum samples from 459 US Air Force personnel involved in aerial herbicide spray missions during the Vietnam War, as well as 459 samples from veterans who served there at the same time but were uninvolved in the spraying missions.
All of these veterans served between 1962 and 1971, when the US military dropped more than 19 million gallons of herbicides in Southeast Asia during Operation Ranch Hand.
Researchers tested for the presence of MGUS and also concentrations of TCDD, a contaminant of Agent Orange that’s been classified as a human carcinogen since 1997.
They found 7.1 percent of Ranch Hand veterans had MGUS, a precursor of multiple myeloma, compared with only 3.1 percent of the comparison group, says Dr. Landgren — a more than twofold higher risk. The risk of getting MGUS was significantly higher among veterans younger than 70 years of age.
The researchers also found that those vets who developed MGUS had higher TCDD levels in their blood samples.
“This provides the first direct scientific evidence that there is a link between Agent Orange and the development of multiple myeloma [in Ranch Hand participants],” Dr. Landgren explains.
The findings were published in JAMA Oncology on September 3.
Wide Use and Exposure
Agent Orange was the most widely used herbicide combination sprayed during the Vietnam War, according to a 2003 Department of Veterans Affairs report. Most adverse events linked to it are blamed on TCDD.
The herbicide was used to protect US troops on the ground by stripping the forests, thereby depriving enemy soldiers of protective foliage. Agent Orange was first used in 1965, according to a 2003 Department of Veterans Affairs report. More than 11 million gallons of the chemical were used as tactical herbicides.
An association doesn’t necessarily mean causation. But, as Nikhil Munshi, a multiple myeloma expert at Harvard School of Medicine, explained in an accompanying editorial:
“Although this study associated risk of MGUS with [Agent Orange] exposure, the fact that all [multiple myeloma] cases originate from MGUS provides the first scientific evidence for a direct link between multiple myeloma and Agent Orange exposure.”
This new research was made possible by previous work Dr. Landgren led at the National Cancer Institute before coming to MSK. He and his colleagues studied data from more than 77,000 participants in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial, who were cancer-free at the start of the study. Seventy-one participants developed multiple myeloma during the study. Dr. Landgren and his team found that “virtually all multiple myeloma cases were preceded by MGUS.”
Previous studies showed an association between pesticide exposure and an increased risk of MGUS and multiple myeloma, but “no studies [had previously] uncovered such an association in Vietnam War veterans,” according to the JAMA Oncology study.
There are real clinical implications to be drawn, Dr. Landgren says, and a very specific group of people can and should be screened for MGUS. Even though not everyone with this precursor condition goes on to develop cancer, his work shows that everyone who has multiple myeloma had MGUS first. Prior work by Dr. Landgren and others shows that the risk of transformation from MGUS to multiple myeloma is about 1 percent per year; for example, 30 years of follow-up equals a 30 percent cumulative risk.
Dr. Landgren emphasizes the value of early detection and suggests that Vietnam veterans get a simple blood test to identify MGUS. That’s because another recent study by Dr. Landgren and co-workers, also published in JAMA Oncology, shows that patients with MGUS who develop multiple myeloma during clinical monitoring have a 10 to 15 percent better overall survival and experience fewer complications than those with multiple myeloma who never received an MGUS diagnosis.