How will a patient know if they are responding to treatment?

How will a patient know if they are responding to treatment? What tests are used to assess response? So there's actually two ways where we can tell if patients are responding. The first and kind of the easier one is patients usually tend to feel better with treatment. So a lot of patients with myeloma can present with bone pain and just general malaise or fatigue among many other symptoms. And so once patients start treatment, they actually report feeling better. And so that's definitely an encouraging sign that we see. In terms of kind of clinical parameters and labs, what we do is we monitor a myriad of And these include blood tests. And among those in the blood tests are like M protein, free light chain levels, immunoglobulin levels. In some cases, we'll monitor the circulating plasma cells in the blood. And then we also look at the urine as a lot of myeloma patients can have this monoclonal protein detected in the urine. And so those are just some of our quicker tests that we can order to tell if a patient's responding. And what we're looking for in those tests is generally a decrease of those variables. So a decrease in the M protein, a decrease in what we call the involved serum free light chain level. So we look at the absolute levels and we look at the ratio. And so we look for normalization in the free light chain ratio and we look at a decrease in the involved free light chain level. And then in terms of imaging, sometimes we'll get imaging, especially if patients have known bone involvement, lytic lesions, which is a common term that we use that's just referring to holes in the bones. So if patients present with lytic lesions, we tend to follow those longitudinally and we try to look for improvement in the lytic lesions and certainly no expansion or no new lytic lesions. And then finally, if we're looking at patients who have extra medullary disease or para medullary disease, that's referring to almost like a plasma cell tumor called a plasma satoma, which can usually grow proximal to the bone or in some cases it can be far away from the bone. Patients present with something like that. We look for disappearance of that or regression in the size of the plasma satoma. Now, how do we determine once you've started on therapy, there are several ways to assess how you're responding. The simplest way is via blood. If you have secretory disease, a very small percentage of patients do not have secretory disease where they don't produce the immunoglobulins or the light chains. For the vast majority of patients, we can monitor disease via blood. We can check serum immunoglobulins. We can check serum light chains, that serum-free kappa light chain, serum-free lambda light chain, as well as your serum protein electrophoresis. And the degree of decrease with each cycle of therapy sort of tells you the sensitivity of your disease to that treatment. So I typically check that monthly in my patients. And sometimes when I'm concerned that the treatment may not be working effectively, I can do that multiple times, but generally it's once a month. And once we know that you've had a complete reduction in your light chains as well as your serum protein electrophoresis, the monoclonal component of that, then or if you're a young patient you might have discussion about stem cell transplant. You can undergo a bone marrow biopsy at post-induction therapy, generally four to six cycles, to assess for the bone marrow plasma cell burden as well as assessing for what is called minimal residual disease, which is already a hot topic amongst clinicians and how we sort of utilize that in guiding patients about therapy. When we treat patients with multiple myeloma, we typically follow some marker of the disease in the blood or in the urine to help us understand how the disease is responding to therapy. For most patients that's an M-spike, which is a monoclonal immunoglobulin in the blood, that's usually an IgG or less commonly an IgA protein. There are much less common ones as well such as IgD. About 20% of patients don't have an M-spike but have other markers like an elevated serum-free light chain level, either kappa or lambda, or elevations of light chains in the urine which can be used to measure their disease. Light chains are actually fragments of antibodies, so all of these proteins are produced by the cancerous plasma cells. Regardless of what the marker is, we track it over time as we're treating patients. After each cycle of therapy, we measure the marker and see if it's gone down in response to treatment. We assess the degree of response by how much we're able to lower those markers and ultimately lower the plasma cells in the bone marrow. When we're assessing response for patients with multiple myeloma, there are two broad categories of assessments that we can talk about. We can talk about peripheral blood testing, so just a blood draw either out of a port or out of the veins, and then you can talk about tests that are run on bone marrow. Ongoing testing in the blood tells you if the serum markers are getting better. When you watch those numbers go to normal, you begin to wonder if the bone marrow normalized as well. If you want to be strict about this, to be able to say someone is in remission or has had a stringent complete response, then you would need to do a bone marrow biopsy to test that to make sure that we can't identify multiple myeloma cells in the bone marrow. In fact, we can even be more sensitive now using minimal residual disease testing to see if what we can't detect with our eyes using just a microscope can be detected using much more sensitive specialized techniques. These aren't available everywhere in the United States right now, but they're becoming more common correlated with how long patients survive after various therapies. There's also a role for imaging patients with low dose whole body CT scans, MRI scans, or PET CT scans. Again, practices here I think across the country are variable. It's not so clear how often we should be testing these in patients. My own practice is that in patients who have a high burden of disease within the bone, a diagnosis, I like to follow them up once I see that the disease has responded well to my induction therapy and potentially a stem cell transplant maintenance to see that those bones are getting better. In patients whose myeloma has changed character and is no longer producing a protein that can be tested in the blood, then imaging as part of routine surveillance during therapy is crucial to make sure that therapy is actually being effective. That tends to be an issue that happens later on in the disease course, although there are some patients who will still present primarily with what are called plasma cytomas that are not secreting monoclonal proteins or free light chains that are detectable in the blood. So there are a number of tests that we use to gauge response. In most patients, we use what's called the monoclonal protein or the M protein, and it's also known as the M spike. The test that actually gives you the result is called the serum protein electrophoresis. Think for the majority of patients that what we can use to gauge response, and some patients don't secrete that M protein, so instead we use what's called the serum free light chain. So that basically looks at the one component of an antibody that the myeloma is producing, and we basically gauge that over time. When would you consider doing a bone marrow biopsy to check for response? The easiest way to test response, especially initially when we started treatment, is with the blood markers, the M protein, and the serum free light chains, but ultimately that really is a biomarker or basically something in the blood that has a pretty good correlation to the actual myeloma, but it's important to realize it's not the myeloma per se that we're seeing when we check the blood. Myeloma itself resides in the bone marrow, and so when we think a patient is in remission, for example, after starting therapy, we would take a sample of the bone marrow, and most people notice bone marrow biopsy, and we would check a few things. We would first check to see how many plasma cells are remaining, and then we would check to see if those plasma cells are in fact more like myeloma cells or not, and then in certain situations when we think the patient may be in a deep response, we'll use ultra sensitive techniques to actually look for any myeloma cell, kind of like looking for a needle in a haystack, and what that really means is that using these technologies we can get anywhere from one in a hundred thousand to one in a million resolutions. Again, that resolution means that after looking for a million cells, for example, we can say definitively that there is not even one bad myeloma cell, and we call that MRD negativity, which is a short for minimal residual disease. How do you assess non-secretory patients for response? Yeah, so a minority of myeloma patients will be labeled as non-secretory or have non-secretory disease, and what that means is that these patients can't be monitored through serum-free light chain levels or a monoclonal protein level in the serum or in the urine. So for these cases, we actually rely on a few tests. One of them is a bone marrow biopsy. We really don't like to do bone marrow biopsies unless we absolutely have to. In those patients, we may need to do them more frequently to monitor their disease, and we look for a decrease in the percentage of the plasma cells compared to all of the other cells in the bone marrow. So that's one way. Another way is to follow imaging, like I said before. So these patients presented with lytic lesions, kind of these holes in the bones or plasma That's certainly a way to monitor disease moving forward, looking for a decrease in the burden of either entity. And certainly progression in these patients, you know, we would see maybe an increase in the lytic lesions, increase in the plasma cell percentage in the bone marrow. So those are some ways we can monitor those patients. There are some indirect studies in the blood that we can use to see if patients may be progressing. Those are calcium levels, and so if we don't have another obvious reason for a patient's serum calcium to be high, that tends to be due to the myeloma. So that could be an indicator that the patient is relapsing. In addition to symptomatically, the patients report feeling better with starting treatment. But we don't, we can't rely entirely on what the patient is feeling. We do have to have some objective evidence that we have control of this disease with the treatments we're giving. For non-secretory patients, it is a combination of imaging, bone marrow, and reliability and patient symptoms. So for a patient who has non-secretory disease, this is usually, it's usually detected by imaging. So I prefer a PET scan. I do that at diagnosis, and then once you've done about three to four cycles of induction, I will repeat another PET scan to assess if there's the degree of, if the lytic lesions have responded in their, in terms of their activity. So generally, that's how I will assess a patient with non-secretory disease. In addition to bone marrow biopsies and imaging, how else is disease response evaluated in non-secretory patients? You know, asking for PET scans monthly is obviously not an economical way to assess that or, and it's not even feasible for the patient. My patients are the first ones to tell me if they have symptoms, and I listen to my patients, you know, and they're relying on my patients for their symptoms and having that faith and that relationship that you do with your patients goes a long way. Patients know their body. Patients are the ones who ultimately make the decisions. We are the facilitators of these decisions, and I try not, I try not to be dismissive of my patients. That's a key thing. Your physician should not be dismissive of your symptoms.