COMy 2023 | The role of the bone marrow microenvironment in myeloma disease progression
Paola Neri, MD, PhD, University of Calgary, Calgary, AB, Canada, discusses the importance of characterizing the bone marrow microenvironment of patients with monoclonal gammopathy of undetermined significance (MGUS) to assess the risk of progression to multiple myeloma. Dr Neri explains that immune cell activity in the bone marrow microenvironment and levels of T-cell exhaustion may be better indicators of progression risk than genetics or tumor dynamics. Dr Neri further comments on strategies to harness this information to further develop effective immune therapies. This interview took place at the 9th World Congress on Controversies in Multiple Myeloma (COMy) 2023, held in Paris, France.
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Transcript (edited for clarity)
What I did present is the role of bone marrow microenvironment, especially in myeloma progression, because we’re all wondering why some patients with an MGUS, this premalignant condition, evolve to myeloma and others don’t. So what I was trying to achieve during that ten minutes is really try to understand what makes a patient progress or another, they stay with this precondition forever...
What I did present is the role of bone marrow microenvironment, especially in myeloma progression, because we’re all wondering why some patients with an MGUS, this premalignant condition, evolve to myeloma and others don’t. So what I was trying to achieve during that ten minutes is really try to understand what makes a patient progress or another, they stay with this precondition forever. And the point I was trying to raise is I don’t think genetics or the tumor is what really changed. I will say it’s probably the bone marrow microenvironment because there is a kind of subtle balance that in some patients they’re always constant and allow the myeloma cells to stay under control. In other patients, this unfortunately is not the case. And I thought and to mention the key players that we think in myeloma and in the bone marrow niche are key. And I mentioned, for example, the role of MDSCs, these immunosuppressive cells that they are in the bone marrow and they are unfortunately the ones helping the T-regs to merge or inhibiting, for example the T-cells. Of course I talked about T-cell exhaustion because some patients, because we have this antigenic stimulation present in the bone marrow have these T-cells which are less fit and therefore less proliferative and unable to capture the myeloma. So I think we are just starting to learn how equally important is the bone marrow microenvironment, not just the tumor. So there was of course others, we were talking about strategies to improve immune therapy and among them is of course combination therapy to help other cells, not just the T-cells to help with the response. And you could probably tell from the audience questions too, how everybody is still trying to ask how we can identify the progressor and non-progressor patients, how to define them in routine. And I will say right now we’re still probably at the beginning of learning that, but definitely in a few years probably we will have a signature that we can use in routine practice.
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