Drug Therapies for RRMM Treatment


The panel provides an overview of drug treatment options for patients with RRMM.

Jeffrey Matous, MD: Another very common and I think under-recognized adverse effect from carfilzomib is the post-infusion reaction. The one when they go home and it’s 4 hours later, and they call when they’re chilling, and they have the 102 °F fever and the headaches. Personally, in my practice, we manage that with a bit of steroids when they go home preventively. I don’t know if you have had a similar experience.

Beth Faiman, PhD, APN-BC, CM: Yes. We were on the original studies in 2007, and it was 20/27 mg twice weekly. That study had just 4 mg of dexamethasone as a premedication, and they had a postmedication. We tried to start them on Mondays or Tuesdays, and that is continued so that on the weekends they’re not running into trouble and calling the on-call folks. I’ve had some severe headaches in some of our patients that I’ve managed with a low dose of gabapentin at bedtime, believe it or not, in addition to the steroids. That’s probably only about 1% to 2%, but there have been patients. For those patients, we slow the infusion, and we do the twice weekly rather than once weekly.

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Jeff, what is that dexamethasone dosing you’re doing with carfilzomib?

Jeffrey Matous, MD: The answer is yes. Typically, if I truly try to get a response, I’m a 40 mg-a-week person, so 20 and 20 mg on each of the 2 days, but after a while, most patients begin to complain about that. We could have a whole different discussion about how to manage dexamethasone adverse effects that would keep us here for the weekend, but that’s normally what I do, and then I see how patients tolerate that. Now in older people, I extrapolate from IMiD [immunomodulatory drug] data where I cut the dexamethasone dose in half.

Let’s talk a bit about pomalidomide because it has been around a long time, but I’m not convinced that everybody out there is comfortable using pomalidomide. Are there any unusual pomalidomide adverse effects that we should be cognizant of?

Beth Faiman, PhD, APN-BC, CM: Neurocognitive changes. Pomalidomide was approved in 2015 in combination with dexamethasone, and there have been several studies since then in combination therapy. But the recommended starting dose tends to be about 4 mg no matter what. With selinexor, the recommended phase 2 dosing is 60 mg of selinexor and pomalidomide 4 mg. In almost every study it’s 4 mg, but patients don’t tolerate it, especially in relapsed disease in combination therapy.

Jeffrey Matous, MD: And older patients.

Beth Faiman, PhD, APN-BC, CM: Especially the older patients. The nice thing about pomalidomide is it’s taken the same way as lenalidomide. Patients are used to taking it on days 1 through 21 of a 28-day schedule, which is very common for nontransplant patients, so you have that comfort, and similar adverse effects such as the increased DVT [deep vein thrombosis] risk, increased risk of cytopenias. But I find that confusion, brain fog, neurocognitive changes are really hard, especially on the elderly. I’ll start at 2 mg for very frail people. I’ll go very quickly down to 1 mg or 1 mg every other day. A bit of a drug is better than no drug at all.

Jeffrey Matous, MD: A sprinkle.

Beth Faiman, PhD, APN-BC, CM: A sprinkle.

Jeffrey Matous, MD: Let’s move on to some pretty exciting stuff now. The buzz in our field is T-cell redirecting therapies. Let’s start with you Zahra, and have you talk a bit about what’s the role of BCMA [B-cell maturation antigen] and why we target it, and how’s that playing into T-cell redirecting therapies.

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: Absolutely. I’m sure you’ll do a much more thorough job than me, but I will do my very best. B-cell maturation antigens are heavily expressed on multiple myeloma cells and almost universally expressed. It’s a very attractive target for us, both with teclistamab and CAR [chimeric antigen receptor] T-cell products, that is a very attractive target. But it’s not the only target. We’re seeing other studies, a lot of trials, other antigens, other products, and other targets we are studying. I think it is a very attractive target; it’s not the only target. It’s just the one that is mostly studied now, and we have approvals for it. But it is a very attractive antigen to target.

Jeffrey Matous, MD: Kirollos, any further comments?

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Just about BCMA too, the attractiveness of this specific target, it allowed us to develop therapeutics that work completely differently. Your bispecifics are engaging a T cell and activating that T cell.

Beth Faiman, PhD, APN-BC, CM: Ahelping hand in bringing them together.

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Exactly. Your CAR T cells are still inducing that immune response. Your ADC [antibody-drug conjugate] that we had on the market uses BCMA to internalize within the cell and then have some cytotoxic effects. I think that target has been very attractive because it can induce so many different types of responses within myeloma. I do know there have been a lot of other very exciting targets, and a lot of clinical trials ongoing. Jeff, I know you’ve had some experience with those. What’s that looking like for you guys?

Jeffrey Matous, MD: They’re great. When I meet with a patient, I draw a little plasma cell with the eccentric nucleus and the Golgi apparatus.

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: I knew you’d do a better job of explaining it than me.

Jeffrey Matous, MD: Idon’t always put the Golgi in there, but I list some of the antigens on the outside of the cell that we’re targeting and let them know, because patients with myeloma always want to know what you are going to do if and when this quits working. They always want to know that. They want to know you have a plan for them beyond what you’re doing next. I’ll say, “Look, we have BCMA right now, but we have these other targets on the outside of the cell that we think we can successfully target with treatments that have different names.” They have cool names, right Beth?

Beth Faiman, PhD, APN-BC, CM: Yes, absolutely.

Jeffrey Matous, MD: GPRC5D.

Beth Faiman, PhD, APN-BC, CM: GPRC5D.

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: I love that you do a shoulder shimmy every time you say it.

Jeffrey Matous, MD: Even CD38 is coming. Then the other thing that’s cool is, we’ve been talking about T cells a lot. But other cells are also being engineered to take advantage of the immune system for targeting these things.

Transcript edited for clarity.

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