ASH 2024 | Excess risk of MGUS in patients with Gaucher disease

The monoclonal gammopathy or MGUS or monoclonal gammopathy of undetermined significance has been in the literature for many years at this time. Initially, Jan Waldenström did the first screening studies in the 1960s and he said this is a benign phenomenon. It has nothing to do with multiple myeloma. And Dr Kyle, who’s a clinician for Mayo Clinic, he kept all the records for people that he saw in the clinic and his colleagues saw at the Mayo Clinic. And in 1978, he went through a big pile of these records, more than 500, 600 charts, and found that some of these individuals actually progressed into multiple myeloma. Dr Kyle, who’s still around and has done a lot of work in the field, is such a polite man and a great clinician. So he didn’t want to offend Dr Waldenström. So he said, we really don’t know. So let’s call it undetermined significance. And That’s where this MGUS comes from. We now know that the reason for MGUS, for the most part, is unknown, why people develop it. But there are some risk factors that have been proposed in the literature. I’ve been involved in many of the screening studies over time. I was working with the United States Air Force, CDC, and also the Veterans Administration and the NIH many years ago. We found that individuals exposed to Agent Orange during the Vietnam War, that there is more of the MGUS in those individuals that were exposed to that. We don’t really understand the exact mechanism for this, but we found that there is an excess, and this has been published. And importantly, individuals that have had this exposure have now been given support for health care through government mechanisms. So it’s important to look for risk factors, both for reimbursement for individuals, and it also could provide clues for why disease happens. So we could understand potentially how we could prevent the disease. Another topic that has been discussed includes Gaucher disease. That’s a genetic disease that refers to germline mutations that relate to enzymatic deficiencies that in turn trigger the immune system to have certain features. And you can have measures of immune activation in individuals. So people have wondered, could Gaucher disease potentially be a trigger for multiple myeloma? And there are people that have been followed over time that have developed myeloma and therefore there has been a lot of literature saying yes, you should really monitor and you should put these individuals on treatment for the Gaucher disease to prevent myeloma. So what’s the basis for this? Well, at this point, we have only seen a few select cases or case reports, but there’s not really been any systematic screening study. So I thought about this for many years and I worked together with the Gaucher Center in Israel, where they have a large collection. So with Dr Ari Zimran and his team, we have done a large screening study that we did present at ASH. And we show that indeed there is an excess risk of myeloma precursor disease, or MGUS, in individuals with an underlying Gaucher disease. So I think there is now evidence from a large screening study that this could be another risk factor for the initiation of plasma cell dyscrasia. I should lastly say that we do not know if the risk of transformation from MGUS into multiple myeloma is any different from people that have known risk factors versus cases that don’t have known risk factors. So we cannot make any claims for that. But there is an excess risk on the monoclonal gammopathy in this cohort.

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