Which patients are more prone to infection? Do certain therapies put patients at more risk of infection? Which ones? Why? Are patients who are in remission at less risk of infection?

Which patients are more prone to infections?

So infections and myeloma unfortunately go hand in hand. When patients are newly diagnosed, one of the most common presentations is an infection, recurrent infections because their myeloma cells are making an unhealthy antibody that's not protecting them from the things that normally they would be protected from. And it's suppressing the healthy antibodies.

So now they are actually immunocompromised and they are more at risk for, you know, viral infections, bacterial infections, things like that. After you start treating myeloma patients, obviously the unhealthy levels of antibodies go down, but you're still suppressing some of the healthy plasma cells as well. So you're still not getting an appropriate level of healthy antibodies in all patients.

Do certain therapies put patients at more risk of infection? Which ones? Why?

And certainly when you're doing things like autologous stem cell transplant, you're really going to have very, very low levels of antibodies and other immune cells. So that's when their patients are extraordinarily immunocompromised and at high risk for infections, and should they get an infection for it to be, you know, aggressive and potentially, you know, really challenging thing to treat.

That being said, certain therapies are certainly more likely to cause or to immunosuppress and make people more susceptible to infections than others. The biggest offenders are typically daratumumab, which is an anti-CD38 antibody that certainly predisposes patients to what we call sinopulmonary infections, viral infections of the nasal, sinuses, chest. Other ones are the BCMA targeting therapies, the CAR-Ts, and the bispecifics. The GPRC5D bispecific antibodies don't seem to be quite as immunosuppressive as the BCMA, but certainly- we certainly are concerned that that could have a longer term risk of infection as well. Those would be the major ones.

And then, of course, anyone coming out of transplant or anyone coming out of traditional, what we call cytotoxic chemotherapy. So these are things like cyclophosphamide or PACE based therapies. Those types of treatments will affect all the immune cells, not just the plasma cells, and certainly will predispose patients to having more immunosuppression. Dexamethasone at high doses certainly is immunosuppressive. The thing for myeloma patients is getting it dosed weekly, which is the traditional dosing regimen for dexamethasone for most myeloma regimens, once or twice a week is not nearly as immunosuppressive as being on dexamethasone chronically. In fact, when they looked previously, when they did persistent dexamethasone dosing, daily dexamethasone dosing, actually there was an increased risk of death and it was typically from infection. So when they backed it off to once or twice a week, that risk went significantly down, but the benefit was maintained. So, dosed correctly, dosed the way that we traditionally will dose dexamethasone with most myeloma regimens in this day and age, that's not as immunosuppressive some of the other agents.