Nikhil C. Munshi, MD, of the Dana-Farber Cancer Institute, Harvard Medical School, and VA Boston Healthcare System in Boston, MA, noted that previous work by Dr. Landgren established that all multiple myelomas have preceding MGUS, although not all MGUS develop into multiple myeloma.

Of the present study, he said, “The extension of the current work is that Agent Orange exposure leads to higher incidence of MGUS, which then would translate to patients developing multiple myeloma in excess. This study connects some of the dots that were not previously connected.”

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In an accompanying editorial,2 he wrote that strengths of this study “include well-characterized samples, a long follow-up period, and availability of measurements of toxin exposure.”

An outstanding mechanistic question is whether TCDD plays a direct role in development of multiple myeloma, or leads to development of MGUS that then requires additional transformation before myeloma development.

Another question for future research, said Dr. Munshi, is whether genetic or other risk factors can be identified that predispose patients with MGUS to malignant transformation, and if so, whether these lead to preventive interventions.

RELATED: IMWG Revises International Staging System for Multiple Myeloma

This research gives further support to earlier studies that suggested a role for pesticide exposure in higher prevalence of MGUS and multiple myeloma.1,2

Agent Orange exposure also has been associated with other B-cell malignancies, including chronic leukocytic leukemia and non-Hodgkin lymphoma.1

When asked about the clinical impact of his research, Dr. Landgren said, “a major impact is to increase alertness around pesticides and exposure and the potential health hazards,” and urged a “continued focus on trying to identify people with other pesticide exposure” leading to efforts to protect people from negative long-term effects.


  1. Landgren O, Shim YK, Michalek J, et al. Agent Orange exposure and monoclonal gammopathy of undetermined significance. An Operation Ranch Hand Veteran cohort study. [published online ahead of print September 3, 2015]. JAMA Oncol. doi:10.1001/jamaoncol.2015.2938.
  2. Munshi NC. Association of Agent Orange with plasma cell disorder: further evidence. [published online ahead of print]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.3015.