 There is a national conversation regarding the price and affordability of drugs going on. Concerns for value and benefits of medications are challenged by the increasing price of the medications, including the cost of care of myeloma. With the availability of new drugs there is an unprecedented improvement in the overall survival of patients with myeloma.

, with a panel of experts, we will discuss the direct benefits to patients and society, and the associated expenses with the new treatments.

I am Dr Keith Stewart, professor of medicine and a consultant in the Division of Hematology/Oncology, Department of Internal Medicine, at the Mayo Clinic in Phoenix, Arizona.

Joining me today are: Mary DeRome, director of medical communications and education, at the Multiple Myeloma Research Foundation in Norwalk, Connecticut;

Dr Rafael Fonseca, professor of medicine and chair of the Department of Internal Medicine at the Mayo Clinic in Phoenix, Arizona;

And Dr. Andrzej Jakubowiak, professor of medicine and director of the Myeloma Program at University of Chicago Medicine in Chicago, Illinois.

Welcome all. Let’s get started. We’re going to begin our discussion by talking about newly diagnosed multiple myeloma. Let me start off with you, Rafael. Do you consider today that all myeloma patients should get the same treatment, or are there ways you can individualize them?

 Well, thank you for the opportunity. I do think that treatment has to be individualized to every patient. We do that in many ways, of course, by clinical variables. The obvious ones being whether the patient is a transplant candidate or not. But beyond that, the biology of the disease is dictating what we should be thinking about therapy, how we think about what combinations, how to use maintenance, etcetera. I think more and more we’re approaching a more individualized approach. We’re not 100% there, but the direction is that for sure.

 Andrzej, what kind of tools do you use to decide how to individualize therapy in a newly diagnosed patient?

 Well, traditional, looking at the patient in terms of how the overall well-being is, any presence of comorbidities, which will affect the choices; biological, to check the disease characteristics, risk factors, which are potentially driving some of our choices. And then we are starting to do use additional tools that are emerging as important to our decision making, better formulating who is a high-risk patient versus standard versus intermediate. And that may impact our choices. But I would jump into Rafael’s comment that, to some extent, we are evolving in terms of individualizing therapy in newly diagnosed patients. There was a time when we were very much convinced that patients with good-risk disease could be receiving lighter therapy to save more aggressive treatments for later. And that has sort of evolved, in my observation, through a little bit different approach.

 Let us come back to that in a bit. Mary, you hear a lot from patients. And the MMRF, [Multiple] Myeloma Research Foundation, has been a leader in individualizing therapy. What are you telling patients today about this topic?

 I think one of the most important things that we tell patients is that they really need to understand what their options are at the beginning when they’re newly diagnosed and then also to make clear to their care teams what their needs and their goals are, their therapy goals. Because, clearly, there are some patients who really want to treat their disease most aggressively up front and are less concerned about any [adverse] effects that might occur. Whereas, there are other patients who are really concerned with maintaining at least some quality of life while receiving effective therapy. So that’s something that we really encourage our patients to do.

 Rafael, how much do you weigh genetic prognostic markers versus blood diagnostic markers versus frailty, and age, and comorbidities? How do you balance those things?

 I’m glad you asked. Yesterday, there was a session that I attended, the geriatric assessment of myeloma patients. And I was not aware of this, but when we think about genetics, they explain the average transplant candidate may be, if you’re lucky, 35%, 40% of the variability. As you go into the older population, the bulk of the variability seems to be explained by fitness and comorbidities. I think that we need to bring that into the equation. I think the magnitude of what I saw yesterday was quite impressive, and it’s important to remember that even if you have high-risk markers, it is not 100% determinant. There are patients with good risk who will not have a good outcome. There are patients with high-risk markers who have sustained CRs [complete responses].

 Mary, how much weight do you think patients put on things like, maybe we’ll get to this later, too, but things like convenience and distance, versus just getting the best therapy available?

 I think it depends on the patient and it depends on the resources available to that particular patient.

Individualizing Therapy for Multiple Myeloma Patients

 Andrzej, what is your personal practice in terms of how you start therapy in terms of backbone treatment, what are you doing, combination of drugs?

 For the time being, as practices evolve, we very much reserve our initial choices to triplet regimens. And our top 2 triplet regimens that we use are KRd and RVd. That is potentially….

 So that would be, just to spell out for the audience?

 KRd is for carfilzomib, lenalidomide, and dexamethasone or Kyprolis/Revlimid/[dexamethasone]. And then RVd will be lenalidomide/bortezomib/[dexamethasone] or Velcade/Revlimid/[dexamethasone], as commercial names suggest. So this is initial treatment. In our practice, most patients receive KRd.

 Is that the same? What about people who are a bit older and maybe less able to travel, what do you use in them?

 There is a good bulk of these patients, which in some criteria would be categorized as older and maybe frail, and even distance may be a factor, whom we still offer what we believe is the most active of these regimens, based on evidence so far, which is KRd [carfilzomib/lenalidomide/dexamethasone]. But there are some patients who have….

 So you’re giving KRd to like 85-year-olds?

 I have to say I can see how some patients would be treated that way, but I’m also impressed by how toxic the regimens can be in the very elderly. And it is a challenge because I think on the one hand, you have attention; doctors who pay attention and try to do their best, I think that contributes to good long-term outcomes. But then you have to balance that with tolerance by patients. And it’s not unusual that I would use milder regimens, in some occasions, even doublets in the very elderly. I don’t think I have the answers for that. That’s why I was particularly interested in this session, and I do think we have a gap of knowledge in that patient population.

 Mary, the MMRF [Multiple Myeloma Research Foundation] is tracking, through some of your programs, what people are receiving around the country. What are you seeing in terms of upfront use in younger and older patients?

 We’ve certainly seen an uptick in triplet regimens in all segments of the patient population, which we think is a good thing because certainly our data have borne out that triplet regimens are more effective than doublets. But again, if you’re dealing with this elderly population, which is more frail, there is a significant number of those patients who are still receiving doublets as well.

 I think to wrap up this discussion balancing convenience, toxicity, and potentially efficacy of the regimen, that this is part of the initial discussion with the patient, which eventually is very balanced and eventually helps to select. We are challenging the question of [an 85-year-old patient], probably most of the time I would not use KRd . But I could use for [an 85-year-old] who is fit and who has a goal to live as long as possible, a regimen that is the best. So, if that surfaces during discussion as the primary goal, “I want to be in remission as long as possible, I want to prolong my life as much as possible,” then the choices are driven by that.

 If I could add something else. There’s an abstract, I believe, at this meeting that looked at the data on ASPIRE and ENDEAVOR and broke it by age groups.

 Since many people might not know what those are….

 Of course. Those are 2 clinical trials, phase 3 trials. One of them compares carfilzomib/lenalidomide, and dexamethasone versus lenalidomide and dexamethasone. Dr Stewart was a principal investigator for that trial. And the ENDEAVOR was a head-to-head comparison, also phase 3, of carfilzomib/dexamethasone versus bortezomib/dexamethasone. And the point of that abstract is that as you look across the various age groups, the benefit appears to persist. So I think there’s a lot of head-scratching because on the one hand, I see those results and I go, of course it matters. We don’t want to undertreat patients. On the other hand, you see the importance of fitness, comorbidities, and the toxicity we see every day in the clinic.

 You have to remember, to get on the trial in the first place you have to be relatively fit, right?

 Of course. That’s a very important point that shouldn’t be missed.

 And actually, many of the trials exclude elderly, unfit patients, so we really don’t have good data.

 In this one…they looked at the patients. I believe the last cutoff was over the age of 75. But again, that tension between not undertreating and making sure that we balance toxicity.

 What about monoclonal antibodies? We’re going to talk in a bit about some of the latest data. But have you seen any enthusiasm for those from our patients?

 A great deal of enthusiasm. Patients are becoming more and more well informed, and they’re very interested in immunotherapy, obviously, because it’s such a fantastic area of research right now in oncology. We’re seeing a lot of interest. And many of the education programs that we’re putting out there around monoclonal antibodies and other immunotherapies are very well attended. So patients know that these therapies are out there, and they’re learning about them, and they are asking their physicians about them, which is a great sign.

 Have you had the opportunity to use upfront monoclonal antibodies?

 Not as of yet outside of the clinical trials, but I anticipate we will all be doing that pretty soon. But you see the results of something like the GRIFFIN trial that was presented at the ASH [American Society of Hematology] meeting, which was a combination of daratumumab plus a standard triplet, RVd, so lenalidomide/bortezomib, and dexamethasone. And at least at that point, the depth of the response is quite impressive. So I don’t think it takes a lot of imagination to see the monoclonals being front line.

 What about you, have you tried monoclonals in the front line yet?

 I have and mostly in the context of clinical trials, but to some extent, to maybe answer your prior question with additional comment. My guide for selecting a regimen is, in a way, helped by what would have been the eligibility for a clinical trial. I have those trials. I know what I am looking for. And if patients would have met criteria for enrollment into a clinical trial, that is then discussed in more detail. But of course, that’s a possibility. So we have currently 2 trials that partner antibodies, one KRd plus elotuzumab, and the other is daratumumab. If the patient meets criteria to be enrolled, we treat patients as old as 80+ on one of these trials.

Factoring Age Into Frontline Therapy for MM

When we start using even 3 drugs but particularly 4, it is becoming a very expensive proposition. So, Rafael, do you worry about that? Are you seeing any end in sight to the rising cost of care for these patients?

 I think we should all be concerned, and we should all be mindful of what the expenses are of these treatments. I do think that when we talk about the monetary value of these treatments, we have to really talk about value, not only about cost and expenses. Because there’s a benefit that comes of course both to patients and ultimately at the end to society. So how do we calculate that? I don’t think anybody has a perfect answer, but we consider how much you spend. By the way, you consider how much you spend not only on drugs but also on other aspects that have risen as much and sometimes even more, which is physicians’ fees, hospital bills, laboratory testing, etcetera. And then you bring into the question the time of disease control, the prevention of hospitalizations, prevention of blood transfusions, surgery for broken bones, and even from a society perspective, the ability of a person who’s still in an active economic life to go back to work. And this is a very complex topic. Again, I don’t think anyone has the answer, but the answer has to be holistic, has to consider all those challenges.

Mary, I’m going to come back to you because I have lots of questions about how the patients react to all this.

But Andrzej, what do you think about this, rising costs and does that impact your practice at all?

 To some extent it does because I am a member of society, so I have to be responsible to start with. But I think in a really detailed day-to-day practice, not much because I am primarily responsible for helping the patient in the best way I can, the best way I think I can prolong their life, with this objective. But I would jump on this part of the discussion and Rafael’s comments with maybe something [to think about that may be] too optimistic, but I think to some extent is important to mention.

As we are increasing the number of drugs, all expensive, and we are achieving better and better responses with these drugs, which is absolutely something we are amazed about and happy to see, we can potentially visualize, in the near future, the following scenario. That you have patients achieving stringent complete response. MRD [minimal residual disease] is at the lowest level possible, negative, and the patient has received say 12, 18 months of therapy, expensive. But we need to figure out, and I think we are very close, in fact we are working on it, to figure out the endgame. When we can say, OK, this patient has a probability of relapse of less than 10% in 4 years, we can stop. And that may potentially address the issue of cost. Because if we frontload cost, but then patients not only live longer but then they are not even on treatment, not generating more toxicities, that’s the win, and that’s the win we need to work on.

Good point, excellent. So, Mary, what are you hearing from patients with respect to the cost of drugs in the newly diagnosed setting, is it something they’re paying attention to, or they just want to get the best care possible and don’t worry about it?

 Well, I think that what we hear and we actually hear from patients not only from the United States but patients all over the world. And it never ceases to amaze me the fantastic therapies that are available here in the United States that just aren’t available in many countries in the rest of the world, and these patients are suffering. But that availability comes at a price. So in a way, it’s great that these therapies are available, but they are very expensive, and of course some patients do have difficulties paying for them. So we spend a lot of time on the phone in our patient navigation center fielding these calls from patients and providing resources to them where we think we can help. Certainly, many of the companies who manufacture these therapies will enable the patient to purchase it.

 Yes, assistance programs, to be able to get the drugs at a lower cost. And there are also patient advocacy foundations, not the MMRF [Multiple Myeloma Research Foundation, but other organizations that will help patients with their co-pays. So we can connect patients with these other organizations.

I think all of us see this as we travel around the world lecturing on myeloma that there is just great disparity between the United States and many countries, some surprising ones. Certainly, in the United Kingdom, it seems right now to be very restrictive, from my perspective. What resources are available to patients? You mentioned some of them. Where do you direct them to get most information?

 So, first we would probably send them to the manufacturers to see if they might be eligible for some of these patient assistant programs. Again, there’s other patient advocacy organizations that help with co-pays. And then we do a lot of research into insurance, Medicare, Medicaid, the particular insurance that the patient may be on to make sure that they’re taking advantage of whatever assistance is in their insurance program as well. Because some patients don’t really know the breadth of coverage for their insurance, and we connect them with resources that can help them decide and define where their responsibility is and how much assistance they can get.

Are there 1 or 2 key Web pages if patients watching or if our peer community is watching, they could go to to get more information?

 I know the Leukemia & Lymphoma Society [LLS] is one of the organizations that will help with co-pay.

Even beyond that just in terms of disease information. LLS is one, your own organization, presumably.

 If I could just complement, one quick point that is sometimes lost is that there is a big difference in whether the patient gets a medication through government programs versus private payers. Anyone who is in a private payer is eligible for one of those various co-pay assistance programs, most of which can limit the payments per month to the range of $20, $25, $30, and some of them have a cap on income. But when you look at patients with Medicare, that’s where there is a difficulty, primarily because it relates to anti-kickback laws. So the idea was you don’t want to have the copay assistance be seen as an inducer to use that.

Now, unfortunately, for our patients, if you need pomalidomide, you need pomalidomide. It’s not like you’re going to choose between pomalidomide and maybe I’ll try melphalan again. You just don’t do that. So it really puts the patient in the middle. I think we should have a very intense and stringent debate about how we deal with this. But between the policy people, in my opinion, if we could remove this from the bedside, I think if patients were spared that stress. Because in our center we can figure it out, but if you’re being cared for in a smaller practice and the support staff or the doctor don’t know about this, there is a possibility that you would forego treatment just because the monthly payment was too high.

For the first time in many years, the group that I find are struggling is, actually if you’re below the income threshold, it seems to be not a problem. But there’s a group of people who fall just above that, and they’re really not wealthy people, but they don’t qualify. And they’ve got $1,000 or $2,000 payments every month for some of these regimens. I have for the first time in a long time, patients say they just can’t afford to take the drug. Do we hear that from patients?

Cost Considerations of Multidrug Regimens in MM

 Let’s move away from the economics for a second because it’s more cheerful to talk about other things. What do you hear from your patients, what are they looking for when they’re first diagnosed?

 That is a time when it’s really important for patients to become as well educated as possible on their disease to help them achieve the best possible outcomes, right? So we’ve worked together in a collaborative effort with a number of other research foundations under this umbrella of the Harvard Business School with this Kraft Precision Medicine Accelerator. So the goal of that organization is to really define what the knowledge gaps are with patients, myeloma patients and other patients, cancer patients in general, actually, when they’re newly diagnosed and what do they need to do and what do they need to learn to assure that they’re going to have the best outcomes for their disease.

What we have come up with in this collaborative effort with the other research foundations is what we call the Right Track initiative where we encourage patients to first find the right care team, second, have the right testing done on their disease, third, get on the right treatment for their disease. And then across the board during all of their newly diagnosed phase, share their data with any organization, so that that data can go toward finding a cure. So, for myeloma specifically, it’s very important to find a care team that sees a lot of myeloma patients because we know that myeloma is a very heterogeneous disease and it’s very complicated. And it’s moving very quickly. There are a lot of new developments very rapidly.

So it’s important for patients to see a myeloma specialist, a hematologist-oncologist who sees a lot of patients who can help and really give them the best advice. They certainly can continue going to their community oncologist, but we encourage them to get a second opinion and to consult with a hematologist-oncologist at least once a year. And it’s also very important to get the right testing done because in myeloma, that will certainly help to determine what subtype your myeloma is, which will then inform the type of treatment that would be best for you at that stage of your disease.

 Thank you. Andrzej, myeloma is a long haul for many patients. We give them upfront therapy, but we do expect that they will need therapies in the future. How much does that feed into your treatment decision-making planning?

 It is something that I discuss, and it’s probably the hardest part for patients to accept. They can potentially very easily accept the plan for induction, for example, or even consolidation if they are transplant candidates. The concept of prolonged treatment is more difficult to not only discuss but eventually to accept.

 Do you save drugs for later or do you use all your best drugs up front?

 I use the best drugs up front, to directly answer this question. I think that the data support that. There are 2 key observations in recent years that I think are supporting that. Number 1) There was, starting from the FIRST trial but several other studies kept showing that if you stop treatment shorter than treating up to progression, you may harm the patients, at least the duration of remission. And number 2) It is important for outcome, statistically, it doesn’t always work for every patient, but it is important statistically to achieve deepest response. There is no question that the deepest response is providing statistically longer remission. And you combine this together because you cannot get to deepest response with short treatment.

Achieving the Best Outcomes for Patients With MM

 Talking about length of treatment now, which also has of course economic implications, what’s the impact of maintenance therapy in your practice, Rafael?

 I think we’re, at this moment, in a situation where maintenance is a standard of care. A few years ago, we were debating this. We sometimes had long conversations with patients. I think unless there’s a contraindication, the results of the meta-analysis from the 3 large trials of maintenance would suggest that lenalidomide maintenance is a standard of care for suitable candidates, post-stem cell transplant.

 So the differences are, I think the data are solid, for lack of a better word, in PFS [progression-free survival]. So you’re talking about 53 versus 23 months of progression-free survival with maintenance. There was an analysis on overall survival improvement of about 2.5 years. I think that’s a little bit less stable because of the number of patients who are out there in that portion of the curve. But the benefits are undoubtedly there. One of the key aspects, I heard this yesterday and I really like the concept, I think for the long-term survival of myeloma, the time to the first relapse is probably one of the most important variables. And that’s why you cannot hold back. You have to put the best team right from the get-go, get your best drugs aligned, and try to maximize that time. Because, as you go through the subsequent lines of therapy, you see that they get shorter and shorter. I call it….

 And that’s another important factor. If you go through one line of therapy, you may not make it to the next. We have data of our own. We presented that last year at EHA [the European Hematology Association] and are submitting the paper, 50% per line of therapy for the transplant-ineligible, a little bit less for the transplant-eligible. But others report 50%.

 Never make it to the next line. If someone says A + B is better than A, a reasonable hand in the audience would say, wait a minute, you should try A followed by B. A reasonable hypothesis, but it needs to be tested because there may not be time for B to be used.

 Putting your societal economic hat on again, do you treat with maintenance indefinitely or do you see that there’s an endpoint where the cost-benefit ratio starts to diminish?

 The short answer is we don’t know. I always make my decisions based on what I think is best for the patient, and I let others decide what’s good from payers’ or society perspective. I think there’s a reasonable argument to be made that time-limited [therapy] may be sufficient. I am hopeful that in the near future, as we bring in MRD [minimal residual disease] testing, that we’ll be able to truncate therapy at the time when we think there’s a sustained MRD-negative status that would allow the patients to be spared the toxicity of maintenance.

 What’s your own practice, do you keep people on forever or do you stop after a while?

 I keep them for as long as they tolerate until there is disease progression.

 Same here. I want to get a sort of patient perspective, although I’m a doctor so I interact with my patients and kind of try to get into their shoes. Some of the points we made earlier—get a good response, treat long so there are good responses achieved&mdash;are eventually rewarded with 2 important things the patient experiences. Number 1) If they do achieve and probability is now 60% or something like that, the disease is not detectable and they go into long-term maintenance therapy, there is this sense of comfort that maybe the disease is really gone and maybe never comes back. “Maybe I am cured.” And we know that this is achievable. That’s number 1. And the second is that they actually are, at this stage of the phase, enjoying normal life on maintenance, and that’s all that they have and almost no or minimal toxicities.

 Do you treat indefinitely or do you stop?

 I do, indefinitely. But because we have such a high pool of patients who achieve this long-standing remission, we are more and more scratching our heads, are we doing the right thing by keeping these patients indefinitely? So in my opinion, our frontier now is to try using new tools, MRD, they have to be refined, to tell the patient are you interested in exploring whether we can stop? And I can tell you, they are all interested.

 Let’s go to you, Mary, because I’ve kind of lost my train of thought there. What are patients saying to you about continuous therapy? Are they comforted by that? Do you feel like they’d rather come off treatment?

 I think that any patient would prefer to come off treatment, as long as their disease is stable and kept under control. We hear from a lot of patients that toxicity is an issue, especially with lenalidomide maintenance. There’s many patients who can’t tolerate that very well. And we know from patient surveys that the question of maintenance is very much on their minds. The question is which drug is the best for maintenance and how long should they be on it? And as we’ve discussed, there really isn’t any hard and fast answer for that yet.

 From what we know right now, it’s lenalidomide. There’s a recent phase 3 trial, the TOURMALINE-MM3 trial that addressed whether ixazomib, an oral proteasome inhibitor, was better than placebo, and it was, but the magnitude of the benefit was not there to suggest that it should be used as a single agent. However, we use it in combination with lenalidomide for high-risk patients. I think there’s very interesting studies going on with daratumumab. But as of now, it’s lenalidomide that’s standard.

 Yes, as a standard of care we use mostly, with few exceptions, lenalidomide. But I would put maybe a little bit of a twist into this comment and practice. We’ve determined that we need to treat patients for a long time because they have a better outcome. And we have younger patients who have transplants. They got 4 or 5, maybe 6 induction regimens, then they go on to transplant, and they are then treated with a single agent, which is we know is not as active as doublets or triplets. We need to explore what we do for these patients, no question.

 In my own practice, I don’t have many people taking single-agent Revlimid. I’ve tended to be adding a second drug, ixazomib, or even bortezomib. I’m looking for depth of response at the same time.

 Yes. It used to just be high-risk but now I’ve started doing it for everybody, basically. A lot of these trials are based on progression-free survival. And just very briefly, before we run out of time here, is that enough, Rafael or Mary, to justify the expense? Do we need to see overall survival before you recommend payment for these medications? Maybe we’ll start with you, Mary. Do we need overall survival or is PFS enough?

 Overall survival would be preferable. But sometimes it can take so long to gather that data, so I think that many people are really hoping that MRD will soon become an established practice in the myeloma field. Because that will really help, I think, in determining what overall….

 It’s all about trade-offs. If you want solid overall survival, but you’re going to deny the drug for many years for patients, I’d rather go with the potential that PFS has consistently shown improvement in overall survival across the board in most myeloma trials, and I think that should be used. But I’m like Mary, I think MRD is going to shorten the time to decision making.

 We did just see one, pretty spectacular example, where that did not happen.

 But we don’t talk about the benefits of the ones that we have already treated. When you actually look at the numbers, I think the benefit has far outweighed the risk, given the challenges with the recent clinical trial.

Impact of Maintenance Therapy in Multiple Myeloma

 Let’s move on to the second part of the discussion today, which is again to dig a bit deeper into our treatment of a newly diagnosed patient. What are in the NCCN [National Comprehensive Cancer Network] guidelines for the treatment of newly diagnosed multiple myeloma, Andrzej?

 The guidelines are generated based on mostly category 1 evidence, which is data coming from randomized phase 3 trials. Fortunately, our members of NCCN are very much open to accepting emerging therapies. So they incorporate, usually in category 2A with good evidence from single-arm trials, recommendations for selection of some of the regimens we discussed earlier today. In fact, neither RVd [lenalidomide/bortezomib/dexamethasone] or KRd [carfilzomib/lenalidomide/dexamethasone] have met this level of evidence, level 1 evidence. But that’s eventually guidance, to some extent.

 So is VRd [bortezomib/lenalidomide/dexamethasone] not level 1, based on the SWOG trial?

 It is already level 1, but it is not yet, to my knowledge, approved by the FDA as a regimen. So that’s sort of a little bit of a….

 You were telling me earlier that you find that reimbursement, if it’s on the NCCN guidelines list, you’re usually covered.

 Correct. If there is a more controversial choice at any point of the treatment, and we are asked to discuss with the payer whether this regimen is really acceptable at this time or experimental, and we have a lot of pushback and statements that they are too experimental, then usually it is the argument that this regimen is not in NCCN guidelines and...not published yet. So these are the layers of filtration from payers and to getting the selection.

 Rafael, we talked a little bit earlier about the drugs that are being used, but what is your frontline regimen of choice, so doublet, a triplet, elderly, frail; why in both cases?

 Sure. With the exception of the very elderly or frail patient, I always use a triplet. And I think my choice is now dictated by the recent clinical trials. So, for non-transplant-eligible patients, the majority of them are going to get a combination of daratumumab/lenalidomide, and dexamethasone, which I’m already doing in my practice. I do scratch my head a little bit with a high-risk patient who’s elderly.

 Now, you say you’re already doing it. We’re expecting approval any day now, but you’ve been able to get it?

 I have so far. We haven’t had problems with that aspect of it. The question although is what to do for the high-risk patient. The confidence intervals are right there, so it doesn’t appear to be any different. But the ALCYONE trial didn’t show, which tested the use of bortezomib frontline, benefit as well. So I still don’t think we know perfectly how to treat high-risk in the elderly. Fortunately, it’s a small minority of patients. It’s about 10% of patients in the elderly. In the transplant-eligible patients, my standard now is a combination of carfilzomib/lenalidomide, and dexamethasone, usually for about 4 cycles and then move on to stem cell transplant.

 Mary, a patient perspective, we covered it a little bit earlier. But do you see preference for triplet or doublet therapy or one drug class over another? Are people worried about toxicity, or is that not important to them initially?

 Certainly patients are worried about toxicity. Again, some patients really want to hit the disease as hard as possible and they’re not as worried about toxicity. Whereas, others are really more interested in maintaining some quality of life, so they may accept something that maybe has less toxicity for them.

 What about transplant, how do patients react to transplant? Are they still nervous or are they mostly accepting it?

 I think that there’s this sort of new generation of patients who are actually beginning to question upfront transplant. And there is a lot of data emerging that some of these newer therapies that we have available are so effective that patients are, in some cases, electing to delay their transplant. They’re collecting cells, but they’re delaying the transplant.

 I think that the jury is still out on that.

 The SWOG trial was a large phase 3 trial, not SWOG trial, it was the French that did it. I forgot what they call it.

 OK, thank you. It was VRd [bortezomib/lenalidomide/dexamethasone]/transplant versus VRd [bortezomib/lenalidomide/dexamethasone] alone. It did show substantial ongoing benefit to transplant. Has that impacted your practice at all, Rafael?

 Not really. I still think that for most patients, transplant is still a good option. There is a subset of patients who have very deep responses who may have personal circumstances or preferences that would opt out of transplant, which I actually respect and support if they want to do that. But everything else being equal, I think most patients need to go to transplant. Maybe we’ll talk more about the FORTE study, too, that is being presented.

 Thank you for that intro because I was going to go right there, actually. So the FORTE trial, which is a very interesting trial, is being presented at this meeting. This is trial of KRd, your favorite regimen, carfilzomib/lenalidomide/dexamethasone, continuously versus the same regimen interrupted to do a transplant. Tell us what that’s showing so far, Andrzej.

 We will see the presentation, but from the abstract and previous presentation at least from this study, there are 2 main observations. First, that [carfilzomib/lenalidomide/dexamethasone] is superior statistically compared to KCd. C stands for cyclophosphamide.

 That’s right, there’s a third arm on that trial.

 And both groups of patients receive exactly the same treatment, 4 cycles before, 4 after transplant, and transplant in middle. And there was a third arm, [carfilzomib/lenalidomide/dexamethasone] for 12 cycles with patients collecting stem cells but not receiving transplant. To some extent, surprisingly, the difference in depths of response and in the level of the deepest responses was very comparable between 2 arms, indicating that possibly you don’t need transplant if you extend [carfilzomib/lenalidomide/dexamethasone]. This was the 12 [cycles], longer, so 4 cycles more. But from the abstract, and we need to see the details, it appears that the group of patients who have potentially increased risk, there is a prolonged duration of remission if you incorporate transplant into the treatment strategy, which is in line with what we have previously seen with [carfilzomib/lenalidomide/dexamethasone]/transplant/[carfilzomib/lenalidomide/dexamethasone] followed by [carfilzomib/lenalidomide/dexamethasone] without....

 We were all quite excited at the ASH [American Society of Hematology] meeting that this was the beginning of the end of transplant if you could give [carfilzomib/lenalidomide/dexamethasone] for 12 months without a transplant. But it looks like that’s beginning to slip now and transplant is still…is that your interpretation of the abstract?

 Well, as we both know that statement, if true, is not because of what’s reported, just because the numbers are small, so it needs to be validated. The data would suggest that the early relapse is prevented by transplant. So the question is, is a CR [complete response] the same as a CR? In other words, is the CR of transplant different from the CR that we get from other treatments? Historically, we know that patients can go into a CR that’s very long-lasting without anything else after transplant, which is less common with the medication. So I think that’s why this study needs to mature as fast as possible. Of course, everyone is going to see whatever they want to see. So transplanters will say, see, they’re relapsing. Non-transplanters will point out that, in fact, we may be getting closer to eliminating transplant from myeloma treatment.

 Do you think with daratumumab, we’ll get there? We never really said earlier.  Maybe let me take a step back. Why [carfilzomib/lenalidomide/dexamethasone] and not VRd [bortezomib/lenalidomide/dexamethasone]? There’s no evidence it’s any better. Andrzej, why are you using [carfilzomib/lenalidomide/dexamethasone]?

 There’s no absolute evidence from randomized trials. Two studies are in progress. One, very advanced, ECOG.

 Why are you using [carfilzomib/lenalidomide/dexamethasone]?

 Well, indirect data from studies reported to date, and not only 1 but for [carfilzomib/lenalidomide/dexamethasone], 3 or 4 studies indicate that respective landmarks of activity of regimen are superior for [carfilzomib/lenalidomide/dexamethasone] versus [bortezomib/lenalidomide/dexamethasone], both response rate, depths of response, and duration of response.

 We’ll maybe come back to dosing schedule later. You’ve switched to [carfilzomib/lenalidomide/dexamethasone] recently, too, I think.

 The reason I switched is a story. We have many grateful patients who come to the clinic, say, “Doc, thank you for everything you’ve done for me. By the way, I still don’t feel my feet.” And that is still with a weekly subcutaneous administration of bortezomib. And it’s a trade-off. So it’s peripheral neuropathy versus the risk of increased cardiac toxicity. From what we understand, it’s a little bit less common in frontline.

 Cardiac toxicity associated with carfilzomib. And from what we can tell, also a large part of it is reversible. Now, we do have a phase 3 clinical trial that is going to be reported in the near future, E1A11, that will compare [carfilzomib/lenalidomide/dexamethasone] versus [bortezomib/lenalidomide/dexamethasone]. But I think given that patients are going to live for years, I really don’t want to see that long-term peripheral neuropathy as part of their baggage.

 It’s fair to say though that [bortezomib/lenalidomide/dexamethasone] remains a sort of backbone in much of the country, outside of academic centers.

NCCN Guidelines for Newly Diagnosed MM

 How much are patients doing what their doctor tells them versus researching and saying, “I don’t like the sound of cardiac toxicity or neurotoxicity. I’d prefer 1 or the other?”

 I think that having that level of knowledge is a little bit unusual, but there are certainly patients out there who ask those questions. One of the things we’ve seen in our patient navigation center, and some of the things that we’ve seen online from patients in our Facebook groups, etc, is that patients are interested in alternative medicine and other ways of sort of augmenting their therapies, and that’s a little…

 Of course not. Certainly, our response to that is that if you are interested in alternative therapies, please discuss with your doctor before you try anything. I think, in general, it’s a pretty bad idea for people to think about going off their therapy and using an alternative therapy. So that’s certainly something that patients need to discuss with their doctors up front, and that’s what we encourage.

 What about cost, here? Kyprolis [carfilzomib] and bortezomib are going generic in some countries already—Canada I think, although, I guess still it’s only intravenous delivery, so there’s still the subcutaneous branded product. Do you think that cost will factor in when comparing it? Do you think there’s a big enough difference in favor of Kyprolis [carfilzomib] to justify the increased cost for the payer?

 I think you can answer that 2 ways. If you’re a patient, if I was a patient—and I’ve never been sitting in that chair&mdash;I know today that I would want to get carfilzomib as my preferred treatment. If you live in a country with resources that have to be allocated in a way that it’s different from ours, I would say it’s a perfectly legitimate thing to be using not only that but also CyBorD as an induction regimen.

 Bortezomib combined with cyclophosphamide [and dexamethasone]. I think in the United States, truth be told, if we look at efficacy and toxicity, and I think in a growing number of myeloma experts, the opinion is that KRd [carfilzomib, lenalidomide, dexamethasone] should be the standard induction therapy.

 And to some extent, the FORTE trial is further validating that there is no RVd [bortezomib, lenalidomide, dexamethasone] as a comparator in this study. But both arms, to some extent, are almost mirroring what we have previously observed. To the patient discussion, which I have as making my points, what to choose between 1 or the other regimen, eventually what makes the biggest argument is when they look at Kaplan-Meier survival curves. And I will tell them that with this type of treatment at 4 years, your probability of relapse will be, say, 20%, 30% when we have KRd [carfilzomib, lenalidomide, dexamethasone] and transplant. Those are our data, what we have, versus more than 50% when you go with RVd [bortezomib, lenalidomide, dexamethasone], with or without transplant. This is very much an appealing argument, short of...evidence from randomized trials.

 What do you tell your patients about toxicity of carfilzomib, particularly as it relates to the heart?

 Everything that I know. It’s a hard discussion that I have. I cover everything that I know. In short, there is no question that bortezomib has an Achilles’ heel, as I call it, in the form of neuropathy—which is more than most patients want to take, there is no question about it. That Achilles’ heel for carfilzomib is cardiovascular, cardiopulmonary toxicity. And I tell them that more than 30% of patients will have some subjective impact of this toxicity on how they feel, in the form of fatigue.

 What is your estimate of how common it is in a newly diagnosed patient?

 In about 30% to 40% of patients, there is some level of what we call dyspnea, suppression of…

 Yeah. That’s coming from the studies you have combined. In fact, they are very subtle. We can pick it up by talking to the patients.

 Serious is less than 4%, and with good management it would be less than 4%. That’s what the discussion is. If toxicities emerge, we’ve learned how to do it to avoid being in this 4%. And we also can manage that 30% and have efficacy and not necessarily toxicity, which is unacceptable.

 And we do hear from patients a lot that neuropathy is a very serious problem for patients. I’ve actually heard patients complain that their doctors never really told them how serious neuropathy could be when they were talking about which initial therapy they could go on. It’s a big concern.

 It’s less a problem now, but in the early days, not having the experience, people would keep treating beyond the first symptoms, and that could get pretty bad.

Considerations for Transplant-Ineligible Patients

 I want to move on to the more elderly patients and just ask very quickly with sort of short answers. What’s your go-to regimen for an elderly nontransplant candidate patient, Rafael?

 As of the last ASH [American Society of Hematology Annual] Meeting & Exposition, I’ve switched to daratumumab-lenalidomide-dexamethasone. I use quite a bit of RVd-lite [lenalidomide, bortezomib, dexamethasone], meaning just attenuated doses. It’s always the dealer’s choice how we do that, usually lower doses of dexamethasone, usually a lower dose of lenalidomide as well. Those are the 2 regimens that I would say I would use the most, occasionally Rd [lenalidomide, dexamethasone] in the very frail patient.

 And for you? You said KRd [carfilzomib, lenalidomide, dexamethasone] earlier. You sticking with that or?

 Well, if patient in my judgment assessment is too high-risk to go on KRd, I am almost certain I will switch to daratumumab-Rd [lenalidomide, dexamethasone] as my top choice. And flipping between daratumumab-Rd and RVd [bortezomib, lenalidomide, dexamethasone] will be probably what we will be starting over the next year or 2.

 Daratumumab-Rd—you both mentioned that. Just in the 

 recently, the results of the MAIA trial were published. Tell us what that showed, Rafael?

 The MAIA is a phase III randomized comparison between daratumumab-Rd, lenalidomide-dexamethasone, versus Rd, lenalidomide-dexamethasone. Huge improvement in progression-free survival, not yet reached. It’s not completely estimated when that’s going to cross, versus lenalidomide-dexamethasone, which actually turned out to be a good regimen. This is something that obviously has changed the paradigm of how we think about the transplant-ineligible patients because before this, the only study that could get close to it, and doesn’t quite do it, is the SWOG [Southwest Oncology Group] study that you mentioned before, the combination RVd. Short of that, if you look at historic data with melphalan-containing regimens, I’m going to say there’s no reason why anyone should ever get melphalan again, with the exception of people at the international level who may have access to daratumumab because of the ALCYONE being approved as a combination for the transplant-ineligible. The results of ALCYONE are quite good.

 What is ALCYONE? Maybe we’ll, just for variety, have you tell us about that 1.

 Yes, this was a study that was already published, and updates were presented in which previous standard of care in many countries, in most of the European countries, VMP [bortezomib, melphalan, prednisone] for elderly patient. VMP is bortezomib, melphalan, prednisone. It was a comparator, and the experimental arm was VMP plus daratumumab. And it was a very strongly positive study regimen to regimen, VMP was given as approved for 9 months of therapy. VMP plus daratumumab backbone was also for 9 months. But then daratumumab continued, which may be part of the impact of daratumumab for the results, which we have seen. But the study was strongly positive with regard to almost all categories. Progression-free survival strongly improved, depths of respond, MRD [minimal residual disease]—negative disease. That was the first approved daratumumab antibody-containing regimen across multiple countries. So [it’s a] big breakthrough, and MAIA I’m sure is going to follow as the next regimen in the frontline setting.

 Both of you have talked about daratumumab, lenalidomide, dexamethasone in the elderly population. Are you worried that there’s no proteasome inhibitor in the first 2 or 3 years of their treatment?

 I don’t think so. In fact, what’s interesting is that even if you break it down by risk, I said that the confidence interval is there. But there’s not a significant difference from what we see with other proteasome inhibitor-containing regimens. It is big question. I think I mentioned this previously, I do have a question as to what is the optimal for high risk patients. But I think for most patients it’s a perfectly legitimate regimen.

 Mary, are patients worried about or troubled by the infusion reactions or the time you have to spend in a hospice chair to get daratumumab?

 Very much. You know older patients have no patience to sit in a chair for 7 hours, to be infused IV [intravenously] for their first daratumumab infusion. But I think some of the data that have come out at this ASCO [American Society of Clinical Oncology Annual Meeting] around the subcutaneous daratumumab injection is quite promising, and that is really going to be, you know, if and when that becomes an approved regimen, it’s going to be a great improvement, especially for the elderly.

 Well, I think our own center, I don’t think it has caught on in the community yet. After the first 2 doses we go to a 90-minute infusion, which it still takes half a day by the time they come in.

 The same thing here. After we went through cycle per cycle, we go more traditionally but we go to 90 minutes, and then subcutaneous will likely be moving in. But I want to maybe make a quick comment about high-risk disease and maybe a controversial aspect. Should we use proteasome inhibitors in high-risk patients versus antibody? I would agree with Rafael here that we don’t have any evidence that 1 of those 2 partners is better at fighting high-risk disease.

But I would add—and it is coming also at this meeting, and prior meetings&mdash;that ultimately for these people, and it has been shown, we have to pick up the strategy that will bring disease to nondetectability: MRD-negative status.

That potentially supports the choices, which we had discussed at the beginning. Do we personalize treatment or not? I think we should be always thinking that we always help patients with the best regimen no matter what the risk. But we have a responsibility to give patients with high risk as good of a regimen to get them to the high level of response.

 I’m a bit uncomfortable not having a proteasome inhibitor in the mix at all. I think it’s just a matter of time before it’s both drugs, and not either-or. I’m not quite sure what I’m going to do in terms of RVd-lite versus daratumumab-Rd at this point.

 I think we’re going to do daratumumab-KRd-lite. That’s going to be the future, right? The key is going to be just to adapt. And this causes tension because traditionally the outcomes for the elderly are worse, but primarily because the treatments are not as good because the biology of the elderly is usually more favorable. When you look at it, you know instead of looking at overall survival, you look at how close you can approximate your life expectancy.

You could say it should be easier in the elderly, but it has been harder because the treatments are harder to deliver. But now with some of these regimens, I think if you’re diagnosed with myeloma at the age of 75, it’s not far-fetched to think that you’re going to have a near-normal life expectancy. I’m not saying it’s perfectly normal; I don’t have the data to substantiate that. But even what we see with MAIA and then maybe 1 treatment for a relapse, many patients are going to get past their 80s. So we’ll see what happens.

Practical Implications of the MAIA Study for MM

 If we’re using all these drugs together, it’s getting superexpensive for patients—you know lenalidomide, carfilzomib, daratumumab are all very expensive drugs. Do you see a day in sight, Rafael, where we might consider stopping therapy and not continuing it forever?

 Of course. I think that’s the point that Andrzej made before. It’s incredibly important. I do see a future where we’re going to have a fixed duration of treatment that will result in MRD [minimal residual disease]—negative in a substantial fraction of patients. That would allow the treatment to be shorter, and ultimately to be cheaper. And then once the drugs become generic in the future, it will be incredibly cheap. Think about the 2000s, when the first wave of long-term sustained remissions in myeloma came to be.

 We already have evidence this is actually happening. Because to some extent, the IFM/DFCI2009 study had provided a lot of data. Transplant is still needed in the novel era, which I completely value as the most important outcome of this study, and we mentioned it briefly. In the patients who have been treated with or without transplant but achieve MRD-negative status and CR [complete response], when they looked at their survival curves, they were very comparable, not statistically different. That guides us now that we’re achieving this level of response. No matter what you do, getting there eventually gives you that chance. And the probability of relapse for this patient was relatively low, and I think we can narrow that gap completely to 10%.

 Mary, do patients understand minimal residual disease and what its implications are, or is that just a bridge too far for them?

 No, they’re beginning to, and we certainly are concentrating on educating patients in that area, because we really feel it’s a necessary development in the field to be able to use MRD as a surrogate end point in clinical trials and to help guide treatment decisions. We’re trying to prepare them as best we can to understand what those results mean.

 Yes, I am. There are 2 scenarios in which I do it: prognostic at day 100 post stem cell, and I do it in patients who have long-term sustained CRs, on therapy, to have the conversation about discontinuation of therapy.

 We have, as a standard of care, our own...base MRD, which is aspiring to be EuroFlow flow level, 10

. We are tuning it up. But for the most part, because we run all these patients who are on trials also single...

 You’re not using moleculars that much?

 We are. Most of our patients are on clinical trials. I actually have for most of our patients 2 results. Both flow and next-generation sequencing. There is about a 10% to 15% difference that we will have a patient who is MRD-negative by flow, would be still positive by next-generation sequencing. We are about to launch commercial use of that test, which is now FDA approved. We will be using it fairly regularly. Because so many patients in our treatment achieve complete response, they are on long-term maintenance. We believe that at some point we will learn that a patient who has sustained MRD-negativity for a year or 2, or more, will be able to be approaching this question, “Can we stop or not?” In a way we are trying to predict that moment by collecting the data already. I yearly check patients and complete response, and we have this information.

 If I could just expand on that and walk through a logic. If a patient is going to get maintenance, myeloma experts will disagree whether they can get 1, 2 years, or indefinitely. And all those answers are correct by current standards. I think it’s perfectly fine to discontinue therapy in someone who has had a sustained CR with MRD-negativity at 2 or 3 years. The person could have stopped therapy even without doing the testing, but it just adds information.

If someone is struggling with a little bit of toxicity, and they’re wondering whether they should continue or not, and they’re MRD-positive, maybe they’ll want to try for a little bit longer of therapy. On the other hand, if someone has a CR but they’re unsure about stopping therapy, and they get an MRD-negative result at 3 years, I think maybe the person is going to be a little bit more confident. There’s just 1 more bit of information that comes into the bedside to make decisions.

 To be the devil’s advocate here, there’s really no plateau in the curve even if you’re MRD-negative. People are still relapsing. So why are you so confident they can use that?

 Because the argument again goes to how long is a standard duration of maintenance therapy? And if there was no plateau then, you would say no one should only get 1 or 2 years, right?

I would counter that the Spanish group, even before we had maintenance or MRD, does show that CR patients can go into that plateau. Their subsequent publication doesn’t show that plateau. But I think that study that was published in 

 in 2011 does show, as the studies have shown from the University of Arkansas, as we see anecdotally in our clinic, there’s a small cell set of patients, hopefully growing, that will have sustained CRs and never again require intensive therapy for myeloma.

 Mary, when I was at the hematology meeting last December, somebody coined the phrase, “MRD Anxiety,” which we do know is MRD testing.

 I was going to ask you: Are you seeing that in patients?

 I have seen patients who have called and said, “Oh no, I’m MRD-positive,” and they’re handed a number, and they would have no understanding of what that means.

 I’ve noticed the same thing. In fact, it makes me anxious as a physician because it’s almost a curse, because it used to be, “Well, you’re doing really great. Your bone marrow is normal, your blood is normal.” Now you’re like, “Oh, sorry, you’ve got MRD-positive disease.”

 But I wanted to ask a question too. As we’re talking about what’s happening in your centers, which wouldn’t necessarily be considered community care centers, what is happening in the community as far as MRD?

 What I’ve heard the committee doctors saying is that they’re not performing MRD. They understand it, and they understand the value, but I think there’s not enough evidence for them to start adopting it at this point. In fact, even some of our academic colleagues I think feel it’s being oversold and is not to be used for decision making. And what I had Dr Bart Barlogie tell me that 1 day, for example.

 And probably rightly so because I don’t think we have data at the moment, and your comment about no development of the tail of that curve is a good argument that we haven’t gotten there. But we haven’t really addressed 1 important issue. MRD is a big basket, which we are sometimes forgetting to maybe define a little better. And there is a different layer of MRD. Any MRD prediction is able to help us with what the outcome will be. You achieve MRD-negativity, and the probability of staying longer in remission is essentially indicated.

, it doesn’t mean exactly the same as 10

. And probably we need to go even deeper, in my personal opinion, 10

 When you look at mass spectrometry, it’s still positive, so it’s kind of depressing.

Clinical Significance of MRD Testing in MM

 I want to move on, because we’re getting close to the end here. I just want to ask sort of rapid-fire here. The 2 trials with daratumumab have been in elderly, nontransplant-eligible patients. How is this going to impact your use of that drug in a younger population, or do you have to wait for RVd [lenalidomide, bortezomib, dexamethasone]—daratumumab trials?

 Honestly, I don’t know what we’re waiting for but I’m still waiting. I’m using KRd [carfilzomib, lenalidomide, dexamethasone] as frontline.

 Yeah. But I’m not sure…people could play around the system. But I think we’ll have the results of the clinical trials pretty soon. And it’s important to know as well, too, that we know that there’s myelosuppression with daratumumab. We see that in combination with IMiDs [immunomodulatory drugs]. I don’t think it’s the case, but we just need to make sure of the whole process of stem cell collection and everything is correct.

 And that there are no infectious deaths to overcome worse than the myeloma.

 Well we have first evidence, which will be presented at this meeting in transplant setting from the CASSIOPEIA trial, which is using a triplet but…

 That was...thalidomide, dexamethasone with or without daratumumab.

 With or without daratumumab, and in transplantation. This is first evidence that daratumumab is improving the outcome in these patients, depths of response, and some other parameters. I think that the writing is already on the wall. We will be using antibody, with triplets.

 Have you started using it? I mean, if I’m a payer though, I’m going to wait for those trials before I pay for it.

 After the clinical trial I would not be able to do it. I will not get approval. But we are in the fortunate position that we have almost every patient segment able to enroll in quadruplet therapy with antibody.

 And are you hearing from patients or other community providers you interact with about where they think daratumumab is going to be in younger patients?

 People are very interested in daratumumab and in the monoclonal antibody therapies in general. I think people are looking forward to that. They know it’s coming, and they’re looking forward to having access to that in the frontline.

 Well, I think what we heard, then, is that both for younger and older patients, triplets are sort of the current standard. We’re hearing a lot of enthusiasm for using daratumumab to replace 1 of the drugs or perhaps add. But we do feel there’s a little bit of a requirement for some more trials to make sure the safety signal is reasonable. I think we also heard from all of you that MRD [minimal residual disease]—negative status is optimal, and it may 1 day give us a reason to not have to treat for years on end if these drugs are as affective as we think they would be.

A Review of the Treatment for Multiple Myeloma

Individualizing Therapy for Multiple Myeloma Patients

Factoring Age Into Frontline Therapy for MM

Cost Considerations of Multidrug Regimens in MM

Achieving the Best Outcomes for Patients With MM

Impact of Maintenance Therapy in Multiple Myeloma

NCCN Guidelines for Newly Diagnosed MM

Considerations for Transplant-Ineligible Patients

Practical Implications of the MAIA Study for MM

Clinical Significance of MRD Testing in MM

Daratumumab in the Treatment Landscape for MM

What Is the Cost of Recurrence in Multiple Myeloma?

Initiating Treatment in Relapsed-Refractory MM

Dosing Strategies in Relapsed-Refractory MM

How Real-World Data Can Address Problems in MM

Backbone Therapy in Newly Diagnosed Multiple Myeloma

Strategy for Up-front Therapy of Multiple Myeloma

Impact of Maintenance Therapy in Multiple Myeloma

FORTE Trial: Transplant in Patients with Multiple Myeloma

Payer Perspective: Transplant and Toxicities in MM Therapy

Long-term Data on Improving OS for Patients With MM

Using MRD Negativity to Stop Maintenance Therapy in MM

MAIA Trial: Transplant-Ineligible Patients With MM

Entering a 4-Drug Regimen for Multiple Myeloma Treatment

The Impact of OCM in the Treatment of Multiple Myeloma

OCM Ensures Better Outcomes and Automatic Cost Savings in Multiple Myeloma

Reimbursement of Subcutaneous Versus IV Dosing in Multiple Myeloma

Treatment Options in Relapsed/Refractory Multiple Myeloma

Patient Cost Implications in Multiple Myeloma Treatment

Managing Discrepancies in NCCN and Payer Guidelines in Multiple Myeloma

Biochemical Versus Symptomatic Relapse Treatment Choices in MM

Final Thoughts on Approach to Multiple Myeloma Treatment