Current and Future Considerations in the Treatment of Relapsed/Refractory Multiple Myeloma - Episode 5

mAb-based Therapies for Relapsed/Refractory Myeloma

March 12, 2021

Considerations for treating patients with relapsed/refractory multiple myeloma with elotuzumab, daratumumab, or isatuximab based on more recent clinical trial data and differences between each treatment option.

Bhavesh Shah, RPh, BCOP: One thing that I feel like we always forget about with elotuzumab is that it’s like the little black sheep in the back. But there are definitely some exciting data that came out at ASH [American Society of Hematology Annual Meeting] too. What do you guys think about the elotuzumab-pomalidomide data that came out at ASH. Does that change anything in your practice?

Heather Pound, PharmD, BCPS, BCOP: We use a fair amount of elotuzumab. It certainly is a niche drug. Obviously you can’t use it as a single agent. I also don’t love the elo-Velcade-dex [elotuzumab, bortezomib, dexamethasone] data. I don’t know many people who do, unless desperate times call for desperate measures.

When you look at ELOQUENT-2 and ELOQUENT-3, we’ve really seen a benefit for patients who are maybe on maintenance Revlimid [lenalidomide] after transplant and their numbers are just starting to creep up. You don’t think they’re refractory to lenalidomide or Revlimid [lenalidomide], so you can get away with pushing that dose, adding in elotuzumab, and getting a little further down the road before you need to start adding in additional therapies. It’s similar if we see a rapid progression in their disease and we need to switch them from lenalidomide to Pomalyst [pomalidomide], for instance. The ELOQUENT-3 data are a good niche for that patient population as well.

Bhavesh Shah, RPh, BCOP: It’s a very niche patient population that you see utilize it, so I’m curious. We have the CD38s being approved in almost any combination that you want to use it with. You can use it with the Cytoxan, the proteasome inhibitor, daratumumab, IMiD [immunomodulatory imide drug]—whatever you want to use it with. How do you decide which CD38 to pair with that combination? Ryan, you have pathways. Is the preference daratumumab vs isatuximab in your pathway?

Ryan Haumschild, PharmD, MS, MBA: For some patients who may be treatment or a transplant ineligible and we start them on therapy, potentially we use CD38 of daratumumab first. We have seen great success with that. Elotuzumab could come back later. If they progress on it and we need something for a later therapy, we may be able to add elotuzumab or another CD38. Typically daratumumab has been our therapy of choice as we start to outline the pathways and then see that deviate as further lines of therapy come up.

Bhavesh Shah, RPh, BCOP: There is some mechanism-of-action difference between daratumumab and isatuximab. They’re both CD38, but we know there are some minor differences. If we look at some of the trials with isatuximab vs daratumumab, there were more patients with renal dysfunction in the isatuximab arm. There was also a clearly defined patient population with COPD [chronic obstructive pulmonary disease] and the isatuximab arm. From your perspective, or maybe your provider’s perspective, is there a difference between these specific conditions and patient population? is there a benefit there where providers may be reaching for this? Where are they using isatuximab? That is my main question. Are folks using daratumumab for everybody?

Heather Pound, PharmD, BCPS, BCOP: We are using daratumumab for everyone.

Bhavesh Shah, RPh, BCOP: I was afraid you were going to say that.

Robert Mancini, PharmD, BCOP, FHOPA: I’m going to agree with Heather on that.

Bhavesh Shah, RPh, BCOP: So it’s not even utilized in patients who are refractory to or relapse from daratumumab.

Heather Pound, PharmD, BCPS, BCOP: That’s like the foot in the door for isatuximab. They have a handful of people who had been on prior CD38 therapy. So they got their foot in the door with that, potentially for people who have relapsed on daratumumab. If you’re concerned about chair time but don’t want to go the subcutaneous route, isatuximab also has the benefit of having shorter infusion times compared with first- and second-dose daratumumab.

Bhavesh Shah, RPh, BCOP: One of the things that I saw at ASH was a distinct cost difference between isatuximab and daratumumab. Depending on the weight category you’re looking at, there’s some real-world evidence that also shows that dose escalation happens with daratumumab. You have the shrinking of the frequency.

So when you look at the real-world evidence, a high number of doses of daratumumab are prescribed because some patients are switched from every 8 weeks to 4 weeks or 6 weeks depending on the stabilization of the disease they have. It’s really interesting. I don’t know if anybody else wants to share another perspective on that.

Robert Mancini, PharmD, BCOP, FHOPA: Going back to something Ryan said earlier and to what Heather was just saying, we looked at care time. We talked about it in the context of daratumumab IV [intravenous] vs subcutaneous. It’s the same argument we had with carfilzomib vs bortezomib when it came out. With the proteasome inhibitors, there is less neuropathy with carfilzomib compared with IV bortezomib.

By the time that information hit the market, no one was doing IV bortezomib anymore. Now we’re facing the same issue. Heather talked about shorter infusion times, which sounds great but as Ryan mentioned almost, everyone is doing subcutaneous daratumumab. One of the benefits of isatuximab over daratumumab is no longer operationally relevant because most people have switched to something more convenient. One of the challenges with myeloma coming so quickly and changing so quickly is that you study 1 thing and then try to prove benefit with a drug, but then all of a sudden that benefit doesn’t exist because that other drug changed as well.

Bhavesh Shah, RPh, BCOP: Yeah, I totally agree.

Transcript edited for clarity.