What does it mean to be immunocompromised?

What does it mean to be immunocompromised?

There are different levels of the degree of immunocompromised. By and large, most of our multiple myeloma patients are either mildly or moderately immunocompromised. The severe immunocompromise ensues shortly after bone marrow transplant, when patients have undergone high dose chemotherapy and autologous or allogeneic stem cell transplant. That's, by far, the greatest degree of immunocompromised that one can encounter. I'd say outside of that, patients with myeloma that's not being treated, for instance, smoldering, may not have too many infectious complications, and their immune system is probably mildly compromised. Obviously, immunization and vaccination is strongly encouraged for all spectrum of multiple myeloma care. Patients who are actively being treated for multiple myeloma, I would say they're moderately compromised. They do tend to have frequent sinus, chest infections with bacteria, viruses, less commonly fungi. And for this, we frequently employ prophylactic antibiotics, antiviral drugs, as well as, as I mentioned, intravenous immunoglobulin in appropriate patients.

Are there any tests that can be ordered to determine if a myeloma patient is immunocompromised?

That's an important question in multiple myeloma. We know that multiple myeloma is a disease itself. The myeloma cells create the immunosuppressive microenvironment in the body and in the bone marrow. There are limited tests that are readily available in our arsenal, which can be employed to assess the immune deficiency of a particular patient. One of the easy-to-perform blood tests is immunoglobulin G level as well as IgM and IgA. These are frequently suppressed in patients with multiple myeloma due to its inherent immunosuppressive mechanism of action. And so typical pattern in multiple myeloma care is that if IgG and all the other immunoglobulins are decreased, this may call for administration of supportive antibody intravenous immunoglobulin, but this is only indicated in patients who are at exceedingly low levels with immunoglobulin G and have suffered from recurrent infections. I should mention that with the advent of all this upcoming newly developed BCMA therapies, we tend to see more and more infectious risks in patients with relapsed myeloma. So there is a notion in the community that we should be more proactive in the usage of intravenous immunoglobulins.

The other test I would mention that can tell us what's the degree of immunosuppression in myeloma is obviously total white cell count and neutrophil count, which are simple blood tests and can be readily performed, as well as a more sophisticated test called flow cytometry, which can tell us different subsets of white blood cells like T cells, B cells, and other components of the immune system.

That's a great question and a really hard one to answer. In some ways, a lot of our testing that we do routinely as part of our routine clinical practice, looking at quantitative immunoglobulin levels, the total IgG, IgA, IgM gives us an idea, but it doesn't give us the whole picture. Similarly, in our post-transplant patients, we sometimes follow what are called CD4 counts, looking at different subsets of the T cells that are recovering over time. But again, this gives us an idea about numbers, but not about their efficacy.

Actually, a lot of the data that was just being presented this morning here at the International Myeloma Workshop was talking about how in myeloma patients, the immune system reconstitutes or is suppressed and looking at those various subsets and activity profiles of different white blood cell subsets. And that's not something that we're doing in routine clinical practice. So we can get a rough idea by looking at things like the total IgG, and if it's low along with IgM and IgA, and those might be patients that, if they're having recurrent infections, would benefit from IVIG or intravenous immunoglobulins.

Similarly, in patients who have low CD4 counts, especially after transplant, those are the patients who we really do need to prophylax against bacterial infections and something called pneumocystis lung infections, something with Bactrim given on Monday, Wednesdays, and Fridays, for example.

But in the routine cases of patients with multiple myeloma, it's hard to know exactly what we should be doing for these patients on long-term daratumumab, for example, or long-term immunomodulatory therapies. And I think what a lot of us end up doing is just in the patients who end up getting sicker, who have prolonged viral infections, that cold that just seems to never go away, even though the whole family managed to clear it in a couple of weeks, or who have subsequent infections across the year, that we end up coming with supportive methods for those patients in particular so that we're not carpet bombing the entire population of our clinics with antibiotics or something like that, and trying to really target to the right patient.

Unfortunately, we don't have a great blood test right now that tells us what to do or how to select the patients most likely to benefit from these types of approaches.

The role of tests that are commercially available at this time in determining how immunosuppressed patients may or may not be is pretty limited. Obviously, standard blood work, white blood cell count, compartments of the white blood cell count can be useful in identifying primarily toxicities of therapy that can be modified to reduce the patient's risk of infection. But other than those basic labs, which, you know, patients’ oncologists should be obtaining with regularity, there aren't real tests of the degree of immunosuppression. Unfortunately, the best test is whether a patient is in and of themselves getting infections.

What biomarkers can be used to identify if there is a greater risk of infection? So I would summarize by saying that it's the white cell count, the absolute neutrophil count, and immunoglobulin G levels.