Daratumumab With Carfilzomib in Frontline Multiple Myeloma

Keith Stewart, MBChB: It sounds like more and more of our patients might start getting daratumumab up front as part of their induction therapy, particularly those who are not so fit. For patients on daratumumab in the past, would you use it again, or would you switch to cetuximab?

Thomas G. Martin, MD: It depends on the length of administration when you give it for induction in maintenance-based therapy. For the GRIFFIN trial, Peter said that daratumumab is stopped at 2 years and then patients continue lenalidomide. They may be on lenalidomide for 2, 3, or 4 more years before they have disease relapse. In that scenario, those patients are for sure, in my mind, CD38 sensitive. For this patient, I would be fine putting them on isatuximab plus pomalidomide. I’d probably put them on daratumumab plus pomalidomide. If they were on a CD38 when they progressed and when they relapsed, then going from 1 CD38 to the other is not going to be an effective strategy, so I wouldn’t recommend that.

Keith Stewart, MBChB: Anybody disagree with that or agree?

Peter Voorhees, MD: I agree completely with what he’s saying.

Natalie S. Callander, MD: It’s very reasonable. [Winship Cancer Institute of] Emory [University] has presented data about going back and using daratumumab specifically with carfilzomib in people who previously even progressed on daratumumab. They still had a response rate that was respectable in the sort of 27%, 28% range. I would agree with Tom that somebody who’s progressing very quickly on an anti-CD38 antibody probably isn’t going to benefit from either.

Keith Stewart, MBChB: I want to challenge you all on your choice. We’ve talked about using pomalidomide in a lenalidomide-refractory.But there are a couple of trials now suggesting that you can combine carfilzomib with daratumumab and have an IMiD [immunomodulatory imide drug]–sparing regimen in those patients. I’m going to go with the person I think is least likely to think that, which is Noopur.

Nooper Raje, MD: Sorry. I like that combination, Keith. The carfilzomib-daratumumab combination is great. The initial challenge was giving 2 IV [intravenous] drugs, the duration of the treatment when we started split-dose daratumumab. Just this past week, we’ve started using subcutaneous daratumumab as well. That makes it even more convenient. In patients who have very aggressive disease and where you want really good responses quickly, I have absolutely used carfilzomib and daratumumab. The data looked quite good.

Thomas G. Martin, MD: I want to make sure we recognize that at the European Hematology Association [Congress] that Phillipe Moreau presented data from isatuximab, also with carfilzomib, the IKEMA trial.

Natalie S. Callander, MD:Very good.

Thomas G. Martin, MD:With the IKEMA trial, there was a significant advantage to the triplet isatuximab plus carfilzomib and dexamethasone versus the doublet carfilzomib-dexamethasone. The hazard ratio is quite low, 0.5. That was the best hazard ratio for an isatuximab study. It looked very promising too. But I agree with you. That is a great regimen for the patients who have lenalidomide-refractory disease.

Keith Stewart, MBChB: Yes.

Nooper Raje, MD:Just to add, there is a subset of patients who just don’t do well on an IMiD. In that patient population, this combination is actually useful.

Natalie S. Callander, MD: Or they can’t get access to an IMiD for financial reasons or insurance problems.

Keith Stewart, MBChB: We have 2 big trials now: the CANDOR study, which was carfilzomib and daratumumab vs carfilzomib and dexamethasone alone; and the study that Tom just mentioned from Dr Moreau presented of isatuximab, carfilzomib, and dexamethasone vs carfilzomib-dexamethasone. Both positive studies for progression-free survival, both show reasonable tolerability. One thing is they both use carfilzomib, in the conventional way, which is somewhat inconvenient for patients. Many people are still using twice-weekly carfilzomib, and many are using weekly dosing.

Peter Voorhees, MD: I’m using weekly carfilzomib exclusively at this point. When using it with daratumumab, I use the 70 mg/m2 weekly dose.

Keith Stewart, MBChB: Have you had any challenges with that in terms of toxicity?

Peter Voorhees, MD: There isn’t any significant difference in toxicity relative to the twice-weekly. The ARROW study would support that.

Keith Stewart, MBChB: Natalie, what’s your experience?

Natalie S. Callander, MD: We use weekly carfilzomib most often at 56 than 70 mg/m2. You know, the ARROW study obviously is out there. But we only use twice a week if a study requires it.

Peter Voorhees, MD: The dosing of carfilzomib depends on the backbone. If it’s cyclophosphamide or daratumumab based, I use the 70 mg/m2. But if it’s IMiD based, I’ll use a 56 mg/m2 weekly dose.

Keith Stewart, MBChB: What we’re saying in summary is that there are alternatives for lenalidomide-refractory or intolerant patients, which combine 2 of our most active drugs, an anti-CD30 antibody with a very active proteasome inhibitor.

Transcript edited for clarity.