Newly Approved Regimens for Relapsed/Refractory Multiple Myeloma

James Hoffman, MD: Both of us have taken advantage of and been excited about a lot of the advances and new drugs that have been coming for myeloma and some that we’re anticipating in the near future. I wanted to talk through some of these with you for the purposes of this presentation, specifically isatuximab as a new monoclonal antibody in combination with pomalidomide and carfilzomib. Certainly, the CD38 antibody daratumumab is something that we’ve used for years. I’m curious what you think about the addition of isatuximab and what some of the recent data have shown us.

Joshua Richter, MD: It’s been exciting, yet another tool in our tool belt. As you pointed out, CD38 monoclonals have become as crucial to the management of myeloma as Rituxan [rituximab] has to the management of non-Hodgkin lymphoma. And with the recent ICARIA and IKEMA data, ICARIA being isa/pom/dex [isatuximab, pomalidomide,dexamethasone] and IKEMA being isa/car/dex, [isatuximab, carfilzomib, dexamethasone] we have yet 2 more triplet options in the relapsed setting. Both are extremely active regimens, and both have shown excellent activity in Revlimid [lenalidomide]-refractory patients, which most patients in the US progress on Revlimid in the front line. One of the big questions I’m facing, and I want to hear your thoughts as well, is where do isatuximab-based regimens fit after dara [daratumumab]? We’re using at our institution a 6-month washout, so if you got dara/rev/dex [daratumumab, lenalidomide, dexamethasone] early on, and you got another regimen in between, and around 6 months have passed, then we say, well, CD38 has probably re-expressed itself on those plasma cells, and that may be a good time to bring in isatuximab with a different partner than they’ve had before. I’d definitely love to hear your thoughts on it.

James Hoffman, MD: Those are all good points. For me, one of the challenges is, as you hinted at, we don’t have data on isatuximab after daratumumab, and we live in a daratumumab world, where patients are getting exposed on relapse, and some of them now with initial therapy. Certainly it would be nice to know or have some real data on what the response rates are going to be with isatuximab vs retreatment with daratumumab and some of these combinations. Isatuximab has some advantages and disadvantages. It’s IV [intravenous] as opposed to subQ [subcutaneous], which we’ll talk a little about with dara [daratumumab] coming up. There are some cost savings with isatuximab vs daratumumab. I haven’t used isatuximab a lot because I am comfortable reusing daratumumab, but I would say that in patients previously treated with dara[daratumumab] like you said, with a washout period and for whom I’m going to be using carfilzomib, which requires an IV anyway, to me that’s a group of patients for whom it’s very reasonable to use isatuximab as opposed to daratumumab, a slightly different epitope, slightly different mechanism. That’s been the one small patient population where I’ve focused on myself.

Joshua Richter, MD: One of the things you brought up in talking is the incorporation of subcutaneous daratumumab, and I want to hear how that’s impacted your practice and any tips or tricks for anyone.

James Hoffman, MD: As soon as we could, we migrated most of our patients over to subcutaneous dara, [daratumumab], and I would say at this point, 95%-plus of our newly treated patients with dara [daratumumab] are getting the subQ formulation. We have rather good evidence that it’s noninferior to the IV form, and patients appreciate being in and out of the treatment room quickly, and not having to get IV access. For me, it’s been tremendous from a patient convenience perspective. These patients don’t want to spend any more time than they need to in the treatment room. At this point we only have a handful of people who are continuing on the IV for their own preferences. What about you guys up in New York?

Joshua Richter, MD: Exactly the same. The only few people who remain on it were the people who’ve been doing so well for years on the IV, they just don’t want to switch. Like when the pharmacy changes generic, they just don’t want to. But exactly the same. We’ve switched almost everyone over to subQ. Almost every new patient we start on subQ. One thing we do is, for the first time they get subQ dara, [daratumumab] especially if they’ve never had dara [daratumumab] before, we monitor them for 3 hours post-subcutaneous injection in the clinic, monitoring for infusion-related reactions. But again, the rates are relatively low, and once we know they tolerate it, exactly like you said, they come in, they get their injection, and they can leave much quicker.

James Hoffman, MD: We do that exactly the same way. It’s nice to see we’re doing things the same, less controversy here. All of us have been comfortable for quite some time using daratumumab combinations, certainly combinations with IMiDs [immunomodulatory imide drugs] with nice synergy, in combination with bortezomib, and then more recently we have validation that it’s a good combination with the irreversible proteasome inhibitor [PI] carfilzomib. I’m curious what you think about the daratumumab, carfilzomib combination and how you might’ve incorporated that into your practice.

Joshua Richter, MD: Absolutely. The DKd [daratumumab, carfilzomib, dexamethasone] regimen has become a huge bonus for us in that a lot of patients now, whether you’re transplant eligible or ineligible, most people end up remaining on Revlimid as some type of maintenance. And unfortunately, every now and again we see patients with explosive relapses, extramedullary disease, renal failure, things like that. The benefit of DKd [daratumumab, carfilzomib, dexamethasone] is that it’s all parenteral, so you can give it immediately if someone shows up to the emergency department or to the clinic in extremis with a huge relapse. And especially for people who don’t do as well on Revlimid maintenance, where just biologically IMiDs don’t seem to be getting the job done, switching over to a CD38 PI has been great for those types of relapses.

James Hoffman, MD: Yes, I agree completely. Certainly, some of our patients who we want to switch from the IMiD to a PI and they have a background neuropathy or didn’t have a great time with bortezomib early on, carfilzomib offers the ability to give a very potent proteasome inhibitor without neuropathy. I feel the same way, and I look to use it in the same patients, lenalidomide-refractory. In somewhat rapid disease progression, I also think it’s an excellent combination.

Transcript Edited for Clarity