Does the patient's immunoglobulin subtype (IgA, IgG, IgM) impact myeloma prognosis and treatment strategies?

In multiple myeloma, not all cases are the same. And one key difference lies in the type of immunoglobulin, or antibody, that the cancerous plasma cells produce. Whether it's IgG, IgA, or the much rarer IgM, your immunoglobulin subtype can offer important clues about how the disease behaves and how it might respond to treatment. But just how much does this subtype impact prognosis? And could it influence the treatment plan your doctor recommends? In this Health Tree University video, we'll unpack the science behind immunoglobulin subtypes and explore what they really mean for patients with myeloma. Does the patient's immunoglobulin subtype, IgA, IgG, IgM, impact myeloma prognosis and treatment strategies? When we have multiple myeloma, we have a monoclonal protein. That monoclonal protein is coming from an abnormal immunoglobulin. Typically, our plasma cells will produce these immunoglobulins in a polyclonal way, so a little bit of IgG, IgA, IgA, IgE, IgD, in very rare situations. But everybody should have a little bit of everything. When you have this monoclonal production of protein, that's when trouble finds the patient, typically. There are different subtypes, as you mentioned. The most common ones are IgG, IgA, and IgM. Actually in that order, IgG is the most common with the better prognosis. IgA is less common, but we consider it more of a high-risk disease. And with IgM, it's rare. And sometimes we have to make sure that we're differentiating this disease from others, right? Like, Walderstrom's macroglobulinemia, because these disorders can be confused, right? And so although we do consider IgM, Iloma, to be a little bit more of a high-risk disease, it doesn't necessarily change what we're going to do upfront. The treatment for newly diagnosed myeloma, either IgG or IgA, for transplant-eligible patients is going to be a quad backbone, followed by transplantation, for example, and then maintenance. We could consider two drugs as maintenance, especially given the fact that we have newer data that validates that CE38-emid maintenance seems to make more sense. But in reality, it's more of a prediction for us, right? To be more mindful of what's to come in the future rather than to change our treatment strategy altogether. We have other high-risk features, right? Especially the biology, right? Because we have three mutations that will upstage you completely. Translocation 414, translocation 416, and deletion 17P. Translations are clearly high-risk features that will change what we do for maintenance mainly and possibly how do we manage the disease in the real-life setting. But the subtype is not as potent possibly as that. The other factor we consider at the time of determining how to treat your patient is the depth of response. Because now we know that MRG negativity is a very strong predictor for the outcome of the patient in the future. If the patient is MRG positive, they have a higher risk of disease regardless of the biology or the subtype than the patient that is MRG negative, right? So it all depends, it depends on the clinical picture of the patient altogether. When we talk about myeloma, we're talking about a malignancy of plasma cells. When plasma cells are in their natural form, they like to make antibodies. And when you make an antibody, you have to usually use two parts. One part is called the heavy chain, the other part is called the light chain. In humans, we have five different options for heavy chains. And because they're all immune proteins, we call them immune globulins or Ig's. So there's IgG, IgA, IgM, IgD and IgE. The light chains, I like to say went to their fraternities or sororities. We only have kappa and lambda. And basically in our body, we have immune cells that make IgG kappa antibodies and IgG lambda and IgA kappa and IgA lambda and all the different combinations. And yes, sometimes the plasma cells get lazy like me and they don't want to make that heavy chain. They just make a kappa or a lambda. We call that free kappa or free lambda. Now, having one or the other doesn't really change anything in terms of prognosis or treatment. It's just basically what cell became abnormal and what proteins we need to look for. So the most common type of antibodies in our body are IgG kappa. So that's the most common type of myeloma. It's like saying in a room full of, you know, 90 men and 10 women, prostate cancer would be more likely than breast cancer just because there's more men than women. There's just 60 percent of our plasma cells make IgG kappa antibodies. So it's the most common type of myeloma. It just means that when myeloma gets worse for those people, IgG and kappa levels go up and the others tend to go down. So it doesn't predict worse or better. It's just we know what to follow for your individual disease. Do non IgG subtypes have a higher risk of progressing? There is some data mostly about precursor disorders like MGUS and smoldering, that non IgG subtypes do have a slightly higher risk of progressing. So an IgA smoldering myeloma may have a slightly higher risk of progressing than IgG. However, there are so many other more predictive factors like the freelight chain ratio, the amount of M spike, whether or not your other immunoglobulins are suppressed, circulating plasma cells in the peripheral blood. So there's so many other factors that are more influential that that doesn't factor in as much nowadays. Does a certain type present with kidney disease or bone disease? Main difference between the different types is less so with the heavy chain and more with the light chain, meaning, you know, IgG, IgA, they don't tend to have much difference. But when it comes to kappa or lambda, lambda type is far more likely to cause something like amyloidosis. So with the lambda light chains linked together and deposit fibers and organs like the kidneys or the heart or the GI tract. Kappa light chain types don't do this as often, less than a third of the time, but they can. They're more likely to cause light chain deposition disease of the kidney or the heart, which is a little bit different than AL amyloids. So that's really what kind of pushes us towards the differences in the light chains. If you found this video helpful, don't forget to like, subscribe, and share it with others who might benefit.