Relapsed/Refractory Multiple Myeloma: Disease Overview


A historical review of treatment advances in relapsed/refractory multiple myeloma and criteria used to define relapsed or refractory disease.

Bhavesh Shah, RPh, BCOP: Hello and welcome to this Directions in Oncology Pharmacy® Peer Exchange. We are going to be talking about current and future considerations in the treatment of relapsed/refractory multiple myeloma.

I’m Bhavesh Shah, from Boston Medical Center Health System, and I’m joined by my esteemed colleagues for the panel, Douglas Braun from American Oncology Network, Ryan Haumschild from Emory Healthcare, Robert Mancini from Saint Luke’s Cancer Institute, and Heather Pound from Baptist MD Anderson Cancer Center. Today we are going to be discussing topics pertaining to the management of relapsed/refractory multiple myeloma, including the current treatment landscape, as well as the latest data and potential treatment strategies on the horizon. Let’s get started on our first topic.

To provide a little bit of historical perspective on multiple myeloma, when I started practicing in 2003 the only 3 drugs we had were vincristine, Adriamycin [doxorubicin], and dexamethasone. Patients had to be admitted to the hospital, continuous infusion, and the other option we had was transplant. Fast forward 10 years, a decade, and there is significant innovation in multiple myeloma. I can’t even begin to talk about all the regimens we have at our behest these days: the multiple proteasome inhibitors, multiple immunomodulators, multiple monoclonal antibodies.

Then looking at future directions in multiple myeloma in the relapsed/refractory setting, it’s amazing to see all this innovation come to light, especially for such a disease. It’s not as prevalent as lung and breast and colon cancers.

Despite these advances in treatments, we know that we will come across patients who will be relapsing. How do we identify these patients who are in the relapsed/refractory setting, and what are the criteria we use? I’ll turn to our colleague Robert Mancini, do you want to start us off in terms of what do you see in your practice and how do you define relapsed/refractory?

Robert Mancini, PharmD, BCOP, FHOPA: Thank you, Bhavesh. I think one of the interesting things that you mentioned is that trajectory. I remember in 2015 when I gave the new drug update for HOPA [the Hematology/Oncology Pharmacy Association], there were 4 new drugs in myeloma. Those things are coming out every year, we get more and more either expanded indications and/or new drugs and new mechanisms. And so even without all of those things coming in, we still see issues with these patients relapsing. That is what we expect to see in pretty much every patient with myeloma who we’re going to talk about. How do we define that criteria? How do we define what someone is in terms of relapse? Is it based on symptoms, is it based on laboratory test results?

If we look at the International Myeloma Working Group criteria, they break it down into 2 categories. The first is looking at the minimal residual disease, or MRD, criteria, and then outside of that is the standard response criteria, which look at whether they are in a complete response, partial response, and all of those play in that as well. For a lot of our patients we are looking at how can we potentially protract this.

Because at this point, we know that myeloma is not curative. So how do we keep these patients alive long enough, how do we make sure that we are not burning through treatments too quickly? Looking at whether we use MRD as criteria versus symptomatic disease, or their light chain disease, or if they have other types of M proteins, do we follow those as the criteria for when we move onto the next type of treatment? I know for us at least, one of the big things is not just whether they are having a complete response, but even stable disease is important as well. Because if we can maintain their disease, prevent it from progressing, prevent it from potentially getting worse, then at least we are protracting and lengthening the life expectancy, potentially, of these patients.

So for us, and I open it up to the others on the group, what is your definition of relapse? For us, we look at symptomatic disease, and we look at what’s called the CRAB [calcium elevation, renal dysfunction, anemia, and bone disease] criteria. So, are they having hypercalcemia, are they having renal insufficiency issues, anemia, or are there new bone lesions? Those things all play into how these patients present and how we will then choose to move on with these patients. I open it up to the rest of the members and see what you guys think in terms of your experience. Do you treat based on minimal residual disease? Do you treat based on the response rates or other symptomatic criteria?

Bhavesh Shah, RPh, BCOP: Thanks for that, Robert. I think it’s a great point. There are so many different definitions of relapsed and refractory. There is extramedullary disease, and then you talk about biochemical relapse, MRD. I’m really curious to hear also from Heather, how do these patients present in your clinic, and what are you guys using as markers of relapse?

Heather Pound, PharmD, BCPS, BCOP: A lot of what we’re seeing, again, there’s clinical relapse, we’re following their SPEP [serum protein electrophoresis], their urine proteins, as well as are they becoming more symptomatic with regard to anemia? Are they having more issues with renal failure, whether that is from the disease itself or from those elevated proteins? MRD has not really started to seep into our clinics, definitely in the relapsed setting. I think that is more within the context of the clinical trial right now.

One barrier to using MRD status in the relapsed setting would be putting patients through potentially unnecessary procedures with a bone marrow biopsy. Again, we know that multiple myeloma is a heterogeneous disease, and so even within the bone marrow, you can have patchy involvement with their disease status. So I think it’ll be a little bit before we start to see MRD being assessed in the relapsed/refractory setting. But it’s definitely one of those things that we’re looking at up front.

Bhavesh Shah, RPh, BCOP: Thank you, Heather. I just want to throw this out there, is anybody also looking at cytogenetics at relapse, is that something that is standard?

Robert Mancini, PharmD, BCOP, FHOPA: I can comment on that, Bhavesh. I think it’s typical to look at how much it plays into the decision-making, more so in context of how aggressive it could potentially be and therefore how aggressive we want to be with the next line of treatment. But I wouldn’t say it’s the primary driver at all.

Bhavesh Shah, RPh, BCOP: I think that, as Heather pointed out, we don’t do a bone marrow biopsies on every single patient who has relapsed. Especially if you look at patients with myeloma, and being in that age category, it’s not the most optimal thing to do for patients. I think we have to look at a specific patient population that we would be doing this in, and specifically probably more refractory, or if you have extramedullary disease that would trigger something like that, that’s invasive.

I think that’s a general consensus that it’s more biochemical, and that there is stable disease, there are other interventions that we do, watch and wait maybe.

Transcript edited for clarity.

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