What factors should you consider when choosing a treatment regimen?

What factors should you consider when choosing a treatment regimen? So it's very important, you know, when you consider treating these patients, you have three goals in mind. One is to achieve a response, of course. Number two is to maintain the response. And number three is to maintain and improve the quality of life. So you have to think that all in consideration equally when you choose a regimen. So it's not easy, you know, what one factor will decide to help to decide the treatment. So you have multiple factors that need to be considered. In particular, if you divide that, it's patient-related factors like how old is the patient, what is the functional status, you know, what are the other comorbidities, then the disease-related factors like how fast the disease is progressing and what is the disease burden the patient What are the high-risk cytogenetics, if not or yes. And lastly, the treatment-related factors means can the patient tolerate the treatment, the toxidase, if the patient has underlying toxidase already in the comorbidities already that would preclude the patient from getting that particular treatment. So I think it's multiple factors that needs to be considered, but with the goal of those three goals in mind. Yeah, so I think we, you know, I always say that patient-related disease, so if someone has comorbidities or even their personal philosophical goals, what is your goal for life, right? We want to make sure we're aligned in why we're treating. And then I think disease-related, so if someone has high-risk disease versus standard risk disease, that's really important. And then past treatments, so if patients, you know, are in the relapse stage or the relapse or factory stage, I really look at what treatments they did well with in terms of less toxicity, but the ones that work the best, right? So we know that we have so many different categories of drugs and different drugs within each category, that if someone did really well with an imid, then I can use a different imid down the road that I'm probably going to come to first before I do, you know, a completely different therapy. And so those are the three main things that I look at. When we're starting a new myeloma patient on treatment, there's many factors that we consider in terms of choosing the right therapy for them. We certainly look at the patient, his or herself, and see how they are generally. Age, frailty, comorbidities, other medications, dialogue with the patient about their priorities certainly come into play. And then there's some myeloma specific variables that we look at. The stage of the myeloma, how has the myeloma made the person ill, the genetics of the myeloma and associated prognosis, whether or not the patient is deemed eligible or ineligible for a stem cell transplant down the road. We kind of put all of these things together and come up with the appropriate treatment plan. Certainly there are some commonalities to treatment. Most patients will be started on dexamethasone as a steroid, lenalidomide, which is a pill. And then there are proteasome inhibitors like bortezomib or carfilzomib. And there's monoclonal antibody therapy with daratumumab. And it's usually some sort of combination of those medications, perhaps slightly more aggressive approaches in more aggressive diseases in younger patients that are more well able to tolerate them and perhaps more gentle approaches for some others. I think there's sort of things that I feel that are not components that can be flexible and some can be flexible. For example, I really do feel strongly that for the most part, most patients should be on a triplet-based novel combination therapy. So I think that's one of the important starting blocks in trying to sort out and start multiple myeloma therapy. I think initially, I tend to favor proteasome inhibitor and immunomodulatory drug triplet combination or quadruplet combination actually now. So I just kind of want to start off with the average patient who I feel like can tolerate it. For me, the algorithm is really whether I give a combination called, in short, KRD, which stands for carfilizomib, lenolidomide, and dexamethasone, or a four-drug combination that is the traditional VRD regimen in combination with daratumumab. Again, the VRD stands for bortezomib, lenolidomide, and dexamethasone. And why I choose one over the other really has to do with whether a patient's cardiovascular baseline is okay or not. And so what I mean by that, does the patient have uncontrolled hypertension or high blood pressure? Have they had multiple heart attacks in the past? Do they suffer from congestive heart failure? And if they have any of those, then I kind of, even if they're controlled somewhat, I tend to favor the four-drug combination called daratumumab with VRD. Alternatively, if that's not the case, usually my go-to is the KRD triplet combination. So other reasons why you may want to choose one over the other is also if a patient potentially has some baseline neuropathy. So presumably haven't been treated already because it's newly diagnosed multiple myeloma. But as you know, many patients, especially in this age class, could have neuropathy due to more common reasons like diabetes and, again, cardiovascular disease. And so that is the reason why I may choose KRD, which really has significantly less, if any, peripheral neuropathy side effects. So I think most of my patients kind of go through that algorithm in my mind. Every once in a while, unfortunately, we have some myeloma patients that, you know, maybe up, you know, higher in age, 70, 75, I mean, rather 75 plus, 80 years old, and may not be as fit. And when I say fit in terms of functional status, they kind of need help at home and whatnot. So traditionally, these patients were treated with what we call the kind of like Pepsi, diet Pepsi. We call that VRD light. But I think in my practice, and I really feel in most, you know, myeloma centers, most of these patients are being treated by the with the regimen called DRD for short, which stands for diuretumum, amyloid, and linoleumid, and dexamethasone. And that's really based on the MYA study, which showed a significant improvement in progression free survival, which is basically the time that it takes for the myeloma to come back or that a patient dies. And also the overall survival, which obviously is how long a patient lives. So those results were significant enough that I think the paradigm has changed for many people, at least for myself. Then there's, you know, other minor considerations, like for example, patients who may have a lot of renal disease may limit your ability to give the full doses of linoleumide and they could incur a lot of side effects if you do. And so in some of those patients, we may start off with, you know, a somewhat different regimen. For example, we may remove the linoleumide and give them a regimen called Cyborg D for short, which is cytoxan, bortezomib, and dexamethasone. But again, in my practice, I usually try to stabilize them with one or two cycles with and really then try to get them on, you know, an immunomodulatory proteasome inhibitor and or NICD38 monoclonal antibody based therapy. Why would you consider not using Kyprolis in patients who have significant baseline heart disease? The first proteasome inhibitor that was developed was bortezomib or Velcade. And Velcade did work really well, but one of its major side effects was peripheral neuropathy. And one of the reasons for that is sort of its action on cells and other proteins that are not its intended target. So based on that, we developed carfilzomib or Kyprolis, which was actually more specific to what's called a 20S proteasome, which is where these proteasome inhibitors work. And because of that, one of the consequences, and it's a lot more potent than bortezomib, although we did get rid of the peripheral neuropathy, it has a really rare but significant risk of heart problems. So these heart problems can be vast. They can include congestive heart failure. They can include just high blood pressure. They could include cardiac ischemia or also known as heart attacks. And so if the patient is already suffering from that, maybe their cardiac reserve is less, we don't want to take a chance. I can tell you in practice, it takes a little bit of knowledge to know how to administer carfilzomib. So it's also really maybe not for the everyday clinic. And I say that because you do really have to be careful about how much intravenous fluids you do give your patient. If you give too much, then that kind of potentiates the drug's ability to cause congestive heart failure. I think the other thing you have to also be careful about, which is indirectly related to the cardiac problem, is the risk of venous thromboembolic disease, or also known as blood clots, I think increases because carfilzomib, especially in combination with linalytomide, is very potent. And you can get rates as high as 25% of your patients having blood clots. Due to the breadth of new myeloma therapies that have come out in the last decade or so, the mode of administration is quite different amongst them. So we have several oral options, we have several infusional options, we have subcutaneous options, and then there's various combinations of all these medications. So when we're thinking about optimal therapy from a patient perspective, I do think quality of life considerations need to come into play. That could simply be travel related. A lot of patients travel from far away to get some of these infusions. And I think if a potential oral therapy can get them the same benefit with, let's say, a different toxicity profile, that may be preferred as long as the patient and physician are on the same page when it comes to the likelihood of benefit they may receive from an oral therapy, for example, versus an infusional therapy. I also think toxicity from prior therapy is an important consideration from a patient perspective. What I see not uncommonly is patients that have had profound neuropathy from prior bortezomib exposure, a lot of times it's become a part of their lives. They've spent the last several years managing that, whether that's with medications or other methods. And at that time, I feel like sometimes they kind of downplay the impact that might be having on their quality of life. So it's important for the patient to communicate with the physician to let us know what they feel day to day. And because we do have many options now, we could potentially limit or progress further symptoms from developing as they may impact quality of life going forward. Why should an individual get a second opinion before choosing a treatment option? Yeah, I think as myeloma therapy becomes more complex, I think it is important to get different opinions when you're at a point of making decisions about what the next line of therapy might be. I truly believe again that myeloma therapy must be very individualized. And for that, there may be difference in opinions amongst different people about what the next best thing might be for an individual. That doesn't make one option right and the other one wrong. I do think, however, it is important to get all the information and get thoughts from people about why those rational combinations are being recommended for an individual, even if they differ. So it's important from a patient's perspective to understand a thought process that goes in when choosing lines of therapy, because we do think of myeloma as a marathon. So if we are potentially recommending a very active combination, let's say in the first relapse, we also think about what might be available for the patient in the future if they relapse on this recommended regimen. So it's important to think not just in the moment, but also several steps ahead to make sure that we are not potentially eliminating certain options for patients that may benefit them, let's say, at a later time. So I tell people they should think about getting a second opinion every time they feel like they want to get more information. And that by no means is a negative factor on their local physician or their primary oncologist. It really just comes down to your own peace of mind and making sure you fully understand all the medications that we have available and why we might be recommending a particular combination or not. And the second thing I will just say is any time consideration is being given for a particular clinical trial, let's say that's not available at your local facility, I think that's another time to explore at major academic centers to see what is available at that moment for an individual, which may be different because it is in clinical trial format than what might be recommended at the primary oncology with the primary oncology team.