What is meant by immune system status? How is it measured?

What is immune system status? Immune system status has to do with what the patient's overall immune health is. In general, healthy people have a healthy immune status. MGUS, smoldering myeloma, their immune system begins to become debilitated and with myeloma, the treatment becomes even more debilitated. The immune status over time with disease progression goes down. Immune profiling is really more of an analytic assessment of the patient's underlying immune system. That can be done in a variety of ways depending upon how deep you want to look at it. It can be through flow cytometry of certain subsets of immune cells. It can be through genetic analysis of receptors. It can be through a variety of those things. And how and what that actually means is still questionable but certainly has been used to sort of correlate retrospectively with outcomes of patients on immunotherapeutic studies. Is it true that everyone has some type of mutated cell but some immune systems are better at fighting them off than others? So I think the whole role of the immune system in fighting cancer, I mean clearly what we're focused on right now is a patient that has a diagnosis of cancer and how can we elicit this immune system to then go back and eradicate a pre-existing disease burden. But what we probably don't appreciate is this concept of immune surveillance. This concept that we are constantly spontaneously developing cancers and that when the cancer is present at a very small disease burden, one cell, three cells, ten cells, that we can eradicate it. Evidence of this concept of immune surveillance is seen clinically. When you look at patients that are immunosuppressed, patients with AIDS, patients that are solid organ transplanted patients that are on significant immunosuppression, those patients have a much higher likelihood of developing cancer than patients with an intact immune system. And that I think is one of the best clinical evidence that supports this concept of immune surveillance. That if you have an intact immune system, your likelihood of developing a cancer is lower than if your immune system is somehow dysfunctional. Probably the most harmful treatments for the immune system were the classical chemotherapy drugs that we used to give very broadly in myeloma before any more modern therapies were available. These drugs are known to really kill a broad range of immune cells and through that led to immune deficiency that was profound and also very complex. The current treatments are more targeted and the effect on the immune system is therefore more targeted as well. But we have to keep in mind with all the modern immunotherapies, we are actually killing a part of the healthy immune system involuntarily as well. So I think it's something that we need to watch closely as to what longer term effects that might potentially develop. It is very, very clear that when a patient needs a line of therapy, the benefit is always outweighing the risk. But I think there is still a number of unknowns what this depletion of some, especially of the healthy B cell populations, will do in the long run in patients.