Role of Real-World Evidence in the Evolving Treatment Landscape of Multiple Myeloma - Episode 14

MM Unmet Needs

Dr Baljević discusses unmet needs that are typically seen in the management of MM.

Ryan Haumschild, PharmD, MS, MBA: Muhamed, as we look at this education of real-world evidence [RWE], there are still many unmet needs within the treatment paradigm. What are some of those unmet needs? How can we educate practitioners and payers around this so that we have faster adoption? As Roy mentioned earlier, if it doesn’t take us 8 years to get therapy to the market, then we can provide those better outcomes now.

Muhamed Baljević, MD, FACP: Ryan, you mentioned 1 key thing: education. It takes quite awhile for the randomized control data to permeate into community and into the real world. Frankly, in many settings, if we discuss some of these things, we often hear feedback from our colleagues, who say, “I didn’t realize that these data were there. This is going to impact how I use an X driver,” for example. One thing you’re doing wonderfully with this group is bringing attention to some of these aspects and raising the level of understanding and comprehension about some of these complex aspects. We still don’t have an answer, but at least we’re talking about what the best solutions are.

Earlier we pointed out some of the unmet needs. Some rarer forms of [multiple myeloma] are systematically being excluded. Most of the time, they’re the highest presentation. For example, patients with impaired renal function or liver function, with lower levels of performance, are systematically being excluded from the trials looking at novel agents. Obviously, those things raise the risk of a falsely negative trial, and you end up with a significant real-world population that doesn’t have the data tailored to them. Then you start wondering, “That phase 3 trial that was done—is it applicable to patients who you see in the clinic?” Perhaps not as much.

The last thing is that we’re going to have to continue doing what, I would humbly say, we’ve been doing in this field. We must be very proactive, try to walk in line with the times, and maybe even anticipate what the field and our patients are going to need.

Let me give an example. At this point, we’re still waiting for the maturation of some of the clinical trial data on whether some of the modern quads, such as VRd [bortezomib, lenalidomide, dexamethasone]–daratumumab, KRd [carfilzomib, lenalidomide, dexamethasone]–daratumumab, or isatuximab-VRd [bortezomib, lenalidomide, dexamethasone], will be labeled for use in the first-line setting. But after just 1 line of treatment, we’re going to have patients who are potentially triple-class relapsed or refractory.

We said that all these amazing new immune drugs, such as CAR [chimeric antigen receptor] T cells and bispecifics, are increasingly being brought forward, even in the second or first lines. Let’s say they’re going to be used in a second line. They’re going to be powerful. They’re going to give us some benefit. But eventually, like most patients with myeloma, they’ll progress. How do we treat somebody who is triple-class refractory and marrow refractory, for example? There’s 0 knowledge about that. There are 0 randomized trials that have looked at patients who are triple-class plus BC marrow refractory.

What’s the best treatment for them? The reality is, we’re creating that standard…potentially this year. The FDA [has approved] cilta-cel [ciltacabtagene autoleucel]. Hopefully, this year we’re going to hear on 1 of the bispecifics. Maybe it will be approved. Within a few years, we’re going to have to deal with the situation.

Unfortunately, these answers will not be generated easily, with tremendous support from partners from the industry, because sometimes the interests don’t align. It’s going to be on us, as we’re talking about the real-world data, to fill some of these gaps. [For example, maybe] it wasn’t a randomized trial, but we had hundreds of patients treated this way or that way. We do our best in terms of comparing the populations, and we draw meaningful conclusions out of it that can inform how we’re going to treat some of these upcoming challenges. Even now, much less than knowing the best option, we don’t even know what the options are.

Ryan Haumschild, PharmD, MS, MBA: That’s very true. That’s why, as you mentioned, we have to educate ourselves on how we can apply this real-world evidence moving forward. Roy, from your perspective and from payers’, is there still an unmet need in education around real-world evidence? Are people understanding real-world evidence? Are they applying it in the payer landscape? Or is there still hesitation and some further demystifying of the evidence as we make decisions that, at the end of the day, affect budgets and covered lives?

Roy Beveridge, MD: Payers have been using real-world evidence for a number of years and will continue to do so. I support the thesis that RWE in myeloma is particularly important for a couple of reasons. We’ve just talked about the myriad effective treatments that we have. We’ve talked about the high cost. One thing we haven’t talked about, which is important for myeloma, is that the same thing happened in Hodgkin disease and others. If a disease within myeloma is curable or in a maintenance situation for someone for a long period of time, or it’s a situation where someone is going to do poorly, then that changes the pathways. It changes how we look at things. It certainly changes how a payer should be thinking about paying for something.

To Muhamed’s point, if treatments are putting people into maintenance therapy for years and years, then that’s an important person to support. You’re not adding 2 or 3 months in pancreatic cancer or 4, 5, or 8 months in lung cancer. You’re adding years and years of life to people. There’s a moral imperative for people to do that correctly in maintenance. At the same time, in patients who are maybe 80 years old with a long list of comorbidities, and there’s no evidence that people are going to do particularly well, maybe we should be treating them in a different manner. This is the power of RWE in this disease. It’s got the potential for treating patients who are going to do very well to be very aggressive, just like Hodgkin. Whereas in other diseases, maybe we should be a little less aggressive based on associated comorbidities.

This transcript has been edited for clarity.