Hi. I'm Betsy O'Donnell from the Dana-Farber Cancer Institute.

Today I'm going to be talking about a study that we did, which is a retrospective observational study, looking at the use of immunoglobulin replacement therapy in multiple myeloma patients.

So one of the significant problems that multiple myeloma patients face is a risk of infections. That risk is both due to the disease itself, where we see preferential clonal expansion of the clonal immunoglobulin population at the expense of our good polyclonal gamma globulins. And in addition to that, a lot of our more novel therapies in particular cause hypogammaglobulinemia, which is a total reduction in the amount of infection-fighting globulins that we have.

And so what this study looked at was our use of immunoglobulin replacement therapy in patients with multiple myeloma.

And so we identified about 6000 patients, from the MGB patient data kind of vault, so to speak. And what we saw in that is that if immunoglobulin replacement therapy was initiated, that we were able to decrease significantly the risk of infection, particularly significant infections and the risk of antimicrobial use. So things like antibiotics or antifungals, antivirals.

And this is a really important thing to understand, because we know that there's increased mortality from infections in patients with myeloma. So if we're proactive, in our ability to use intravenous immunoglobulins or IVIG, in our patients, then we can potentially mitigate some of the more dangerous complications of myeloma therapies.

There are a couple different standards that are used. So at what point do we initiate the use of IVIG? And so some of our guidelines would call for a threshold of any value less than 400. But what we see and what we see in the data for some of our clinical trials, specifically those with bispecifics where we saw significant risk of infection, upwards of 70%, is that those patients fall between that 400-500 range. So we set a threshold to 500, and demonstrated the significant reduction of risk of infection and antimicrobial use and of hypogammaglobulinemia.

So when we give IVIG we significantly, not surprisingly, improve those outcomes. And so for patients, I think we need to be monitoring, you're having your SPEP on anyway. So we monitor those levels and particularly in those patients who are having infectious complications, then giving IVIG can be extremely beneficial.

That's the total quantity of immunoglobulin G. So when we talk about immunoglobulin replacement therapy, we're specifically talking about replacement with intravenous immunoglobulin G. And so the normal range is much higher than that. Somewhere about 750 is the lower limit of normal. And you start to go too low. You don't have enough of those immunoglobulin G infection-fighting antibodies. And so we give those back. And so that's what this therapy is. So when your total immunoglobulin G level, which is measured through your SPEP, goes below 500, our data support that you are, if you receive IVIG, then your risk of infection goes down significantly.

I think just in general that this was seen across the myeloma spectrum. So this was started this work, we looked from 2010 until 2023, which was really before the mainstream and incorporation of CAR-T cells and before we had any improved bispecifics. So this applies not only to the immunotherapies too, but a lot of our other myeloma therapies in particularly transplant as well.