Current and Future Considerations in the Treatment of Relapsed/Refractory Multiple Myeloma - Episode 4

Backbone Regimens for Relapsed/Refractory Myeloma

March 12, 2021

Variables considered by healthcare professionals when selecting an appropriate backbone regimen to manage a patient with relapsed or refractory multiple myeloma.

Bhavesh Shah, RPh, BCOP: I know we have limited time, and we can probably talk about this for a very long time. I want to, for the sake of time, briefly touch upon, there are a lot of different backbones of regimens that we can use. How does one decide on choosing an IMiD [immunomodulatory drug]-based regimen versus a proteasome-based regimen, and also adding a CD38 on top? Of course, there are other options. I wanted to high-level share some perspectives on how those regimens are chosen in your institution.

Robert Mancini, PharmD, BCOP, FHOPA: I can chime in first, Bhavesh. I think, as we have already pointed out, and Heather talked about at length when we first started talking about this particular topic, is we have to look at what have these patients had before, and how have they done with it? And I think again, are we talking about relapse after transplant, or are we talking about relapse on a current therapy? Because that will change your perspective.

I can’t speak for everyone, but I know that for a lot of the physicians I work with, it’s a habit to try something different. If they were on an IMiD-based therapy, then the next step would be to go to a proteasome-based therapy or vice versa, or bring in a new agent, either the CD38s or the SLAMF7s, or some of the other treatments. I know we’ll talk about some of the other newer agents as well and where they fall into play, but I think at this point, we try to exhaust a lot of those before we move to the newer therapies.

Bhavesh Shah, RPh, BCOP: Yes. Then there are monoclonal antibody-based backbones, and then we have even an all-oral-regimen backbone that people can use. Recently we have seen that the Boston data came out with selinexor moving into the relapsed/refractory setting. I’m wondering how that is changing. We had CD38 in the refractory setting that we were used to. And now we have data from the Boston trial, which we’ve seen significant activity with selinexor in fifth line relapsed/refractory multiple myeloma. I want to get perspectives on that regimen from one of you guys.

Robert Mancini, PharmD, BCOP, FHOPA: For me at least, one of the issues we face, and I’m sure probably Doug or any of our panelists can probably comment on this. Especially with these newer therapies, we have to make sure that we are treating to the indication. Because one of the biggest pushbacks and issues that we face is how the insurance is going to look at these things. I think how their insurance pays is different for some people getting IV [intravenous] therapy versus oral therapies.

And so we need to look not only at No. 1, are we on label, on indication, or at least on NCCN [National Comprehensive Cancer Network] guideline? Versus a lot of these good ones, like you were mentioning the Boston trial, even though the data look good, are we going to get that paid for by their insurance in that combination? You never really know when we are dealing with those newer regimens.

Bhavesh Shah, RPh, BCOP: That is a great point. We talked about what factors go into it, into treatment decisions. We forgot to talk about cost because it’s probably like the white elephant that nobody wants to talk about, right? But no, that is a great point, Robert. What I also wanted to understand is that we know there are some toxicity implications with selinexor. Moving this in the relapsed/refractory, fourth, fifth line, it is more tolerable that, “Hey, this is going to be happening, but there are no other options.” But you have so many other options in relapsed/refractory. Now, is this going to change your practice, where you are going to be reaching for this? Or are providers actually reaching for this in your practice, already, based on the data and having the FDA approval now?

Ryan Haumschild, PharmD, MS, MBA: They are exciting data, Bhavesh, I have to be honest, and we have been watching it closely. I talked about pathways earlier from that pharmacy director perspective, but they kind of go out the door when you are talking fifth line because at this point you are mixing and matching proteasome-based, monoclonal-based, orals. I think you did a good job hitting that. Selinexor is something we are starting to look at more. I wouldn’t say it’s our go-to now for fourth and fifth line, mainly because we want to make sure it’s tolerable for a lot of our patients. But I do think it is something that we are evaluating more and more, these newer therapies, do we move them up?

Is it worth moving up? Can the patients tolerate the adverse effects because we know that these patients eventually will progress. So are we saving enough therapies for fourth, fifth, potentially sixth line, where they still have a chance, and we still have a chance to keep improving their disease? That is where we are. Not complete adoption, but definitely a lot of interest in it. I probably see us adopting a few more patients, but I think we struggle with how soon do we move it up, or do we still keep it as an option next to clinical trials?

Transcript edited for clarity.