AGMT_MM-1: Assessing the oral microbiome in patients with relapsed/refractory multiple myeloma

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Published: 13 Jun 2020
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Prof Heinz Ludwig - Wilhelmeninen Cancer Research Institute, Vienna, Austria

Prof Heinz Ludwig speaks to ecancer about the AGMT_MM-1 phase II trial presented at the virtual EHA 2020 meeting.

He explains that this trial aims to evaluate the association between the oral microbiome and patient characteristics and treatment outcomes in patients with relapsed/refractory multiple myeloma (RRMM), who were treated with ITd (ixazomib, thalidomide, dexamethasone).

But also if the composition of the microbiome differs patients with multiple myeloma (MM) and the general population.

Prof Ludwig outlines the design of the trial ad highlights the main differences found in each patient group.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

This is a study in patients with relapsed/refractory myeloma . Actually we enrolled ninety patients and they were uniformly treated with an ixazomib based regimen, ixazomib thal-dex. They received eight cycles of induction therapy and then one year of ixazomib maintenance therapy, actually which was very well tolerated maintenance therapy.

One of the questions we raised, or the question which we raised in the poster which is presented now is whether there are differences in outcome in patients with different constitutions of the oral microbiome. So there is very little known about the oral microbiome in general and in myeloma in particular so we collected mouth swabs at baseline, actually we collected them at each cycle, but this presentation just shows the baseline diversity of the oral bacterial microbiome. Actually 79 studies were then actually enrolled in the microbiome study, so the DNA was extracted from the mouth swabs and the bacterial RNA was sequenced. One of the measures of a healthy microbiome is the diversity. So you need to have a high diversity, it’s generally considered to be healthy. When we looked at the outcome patients with a higher diversity of the oral microbiome at the first level, they had a significantly longer progression free survival and with the diversity of the oral microbiome and progression free survival was particularly marked in those with the longest progression free survival. So the higher the diversity, the better the progression free survival, it’s a channel of statistical association.

What was also interesting is patients with progressive disease had a reduced diversity of the microbiome. In other words, you need to have a high diversity in order to have a high likelihood for better progression free survival.

There are very interesting studies which have been done by [??]. So they looked at the microbiome in myeloma bearing mice and what they found is that also these mice have progressive myeloma and when you alter the microbiome by antibiotic treatment you may improve the outcome of these mice. This reminds us of what we do in general, for instance in mouth lymphoma. In very early mouth lymphoma you can cure patients by eliminating Helicobacter by antibiotic therapy. In heavy chain disease, which is a plasma cell disorder affecting the gastrointestinal tract, when you use in early stages antibiotic therapy you can improve the outcome.

So in the near future possibly it may be thinkable that in certain situations modification of the microbiome may be used in order to improve the outcome of the disease of myeloma. You can think about stool transplantation, you can think about antibiotic treatment in certain instances and also you can think about using specific bacterial species to impact on the constitution of the microbiome.

These are initial studies and I’m sure many groups will look at this in greater detail. At this time we can say the composition of the microbiome, of the oral microbiome, is associated with progression free survival. The greater the diversity the better the outcome in our patients.