Current and Future Considerations in the Treatment of Relapsed/Refractory Multiple Myeloma - Episode 2

Treatment Pathways for Relapsed/Refractory Myeloma

March 12, 2021

Factors that influence treatment selection for relapsed or refractory multiple myeloma, and suggestions to help streamline decision making and address limitations associated with current treatment pathways.

Bhavesh Shah, RPh, BCOP: We heard about how these patients present with relapsed/refractory multiple myeloma in our practice, and what factors we utilize to identify that they’re in the relapsed or refractory setting, and what testing we need to do. The next step is what treatments do we offer these patients? I’m curious because with treatment, a philosophy in multiple myeloma it that it’s like Baskin-Robbins, you have 31 flavors, and you basically choose which flavor you want for that month or that time period when you’re seeing that patient.

Heather, I wanted to understand, can you start us off in terms of what factors do you guys take into consideration as these patients present in the relapsed/refractory setting? How do you decide what treatments to offer them?

Heather Pound, PharmD, BCPS, BCOP: I think for us, some of the big factors that influence our choice of therapy are what do those original molecular and cytogenetics look like? Certainly based on their performance status, if they have a great performance status and they have some of those higher risk cytogenetics, either at baseline or with their relapse, we might be more apt to use more intensive chemotherapy with a triplet or potentially even a quadruplet therapy at this point. One thing we have to consider is what therapies they have received before. What have they received in the first-line setting? Were they on maintenance Revlimid [lenalidomide] after their transplant?

Did they get a transplant? One of the things I think will be interesting as we move into the future, certainly with the GRIFFIN trial using quad therapies with Dara [daratumumab] up front, how does that change what options we have in the relapsed/refractory setting? We always have to distinguish between the different classes of agents versus the lines of therapy. As you mentioned, we have lots of different flavors of proteasome inhibitors and IMiDs [immunomodulatory imide drugs], monoclonal antibodies, even some of our new BCMA [B-cell maturation antigen] therapies. Identifying is the patient refractory to a drug or are they refractory to a drug class, some of those things are really important that we talk about.

Certainly, one of the last things that we look at is usually the toxicity profile. When we’re looking at again the patient’s performance status and comorbidities, it might lean me toward making certain recommendations. If they have renal failure, either from their disease or from other comorbidities, that might lean me toward having drugs that don’t need to be renally adjusted or followed as closely. If they have significant peripheral neuropathy from medicines like bortezomib in the upfront therapy, or from diabetes, for instance, we might want to stay away from other drugs that cause a lot of issues with neuropathy as well.

And then as we see carfilzomib being introduced into more of the relapsed/refractory setting and potentially even up front, if they’ve got cardiac issues, that might steer us away from having to use that in those patients.

Bhavesh Shah, RPh, BCOP: There is a significant amount of undertaking in terms of deciding what treatment a patient receives. You just listed at least 20 of them right there, going from cytogenetics to age to performance status to previous therapy, toxicity profile. I’m wondering, I don’t think we can stop, I think we can keep going. I want to also think about other things that may be impacting, maybe a little nonclinical. Ryan, you guys have pathways, so I’m interested how pathways play a role in deciding these treatments.

Ryan Haumschild, PharmD, MS, MBA: Thanks Bhavesh. One of the things I’ll say is pathways are huge. In the future, I think for a lot of therapies, pathways are going to be important because more and more we want to make sure we’re providing consistent care, providing care that can be repeatable in other areas, not just the main faculty site but at other locations. And especially when it comes to the disease state of multiple myeloma, there are so many different therapies being introduced. I think Heather hit on that earlier, and also so many patient-specific factors that need to be taken into consideration.

Are these multiple myeloma pathways the silver bullet? Not exactly, but what we’re trying to do is establish at least treatment algorithms that we can generally follow so we can have better predictability of care, more consistent outcomes, more value-based decisions, and ultimately provide a really good patient experience. If we have patients come in, I think they hit on it earlier, look at the CRAB [calcium elevation, renal dysfunction, anemia, bone disease] criteria, cytogenetics. Then we really want to figure out is a patient transplant eligible, are they not transplant eligible? A lot of times that can streamline the rest of therapy.

Then also we want to stratify patients, whether they are either in the high category or standard. We’ll do that basically looking at their translocations to figure out which bucket they will fall in. Then from there, we try to create some consistency. Having a protease inhibitor, an IMiD, or a steroid for someone who might be high category. For someone who is standard, we might just introduce the CD38, an IMiD, potentially the protease inhibitor, and the steroid, and then see how patients respond to that. That would be probably specifically for our transplant-eligible patient population. And then when we look at our patients who are not transplant eligible, we focus in more, and still stratify based on high or standard, but then look at what type of protease inhibitor, again, what type of IMiD and steroid, etc, do we want to treat them with?

That way, we at least have some consistency, because like Robert mentioned earlier, you don’t want to mix and match too much because you might run out of lines of therapy later. Then I think it gets even more interesting as you head down that pathway of treatment, where do some more of these innovative therapies come into play, these BCMAs? Is it necessarily after 4 lines of therapy or after 4 agents? And how do you begin to introduce that? And what do you do with patients with translocation 11;14 who might be in a standard group? Is there a different way to treat them that might be more efficacious?

In summary, Bhavesh, we’re working on standardization of treatments so that we can preserve treatments for later therapy and provide more consistency of care. But like Heather mentioned earlier, there are still a lot of patient-specific factors that we have to consider, with adverse effects that might be patient specific, that might deviate from the pathway. And that’s OK as long as you are providing innovative care to the patient.

Bhavesh Shah, RPh, BCOP: There’s a lot that goes into deciding pathways and creating these pathways. I’m sure pharmacy is heavily involved in helping manage these pathways. We have heard of payers developing pathways, and independent organizations developing their own pathways. Then there are institutions that create their own pathways using the electronic medical record. Kudos to you guys, especially when you have 31 flavors, how do you create a pathway for each flavor, right?

Robert Mancini, PharmD, BCOP, FHOPA: The only thing I would contribute beyond what Ryan said, is understanding, especially with myeloma, that there are data out there, especially with the proteasome inhibitors, that if the patient has responded in the past, there’s still a chance that they could respond even if they proceeded through that therapy before. As long as they are not refractory, just because they’ve relapsed doesn’t necessarily mean we have to eliminate that as a treatment option. Because in the future, those treatment options can come back and have efficacy in that patient population. I think defining the difference between relapsed and refractory here is important as well.

Transcript edited for clarity.