A. Keith Stewart, MB, ChB:There are numerous clinical trials for a novel agent has been added to an immune modulator such as lenalidomide in relapse. The proteasome inhibitors that have been studied are carfilzomib and ixazomib. Carfilzomib is the only drug so far to show that that combination improves overall survival. On the other hand, both drugs improve progression-free survival and both seem to have impact on high-risk genetic patients. Ixazomib has the value of being orally delivered, and has a little bit less chance of serious toxicities. So, both have a role to play.
There are 2 new monoclonal antibodies now available. There’s elotuzumab, which, with very low toxicity, can improve progression-free survival. It’s a drug that I think we see a little bit more useful in the more frail patient, perhaps. And then, there’s daratumumab, which has been, in some ways, transformative. In adding daratumumab to lenalidomide or to bortezomib, it can be highly successful and helpful.
So, as I mentioned, in the United States, because so many patients have taken lenalidomide for long periods, our drug of choice at first relapse is becoming pomalidomide if we are going to use an immune modulator. Pomalidomide is very well tolerated. It has some of the same issues of the other immune modulators with respect to the fact that patients have to be on an anticoagulant of some kind, either aspirin or a more affluent coagulation.
It can cause myelosuppression. Used alone, the dose is usually 4 mg. But often in patients in which the drug is being combined, 2 mg can be used as well or the dose can be deescalated to 2 mg and still be very successful. In my experience, it’s quite an easy drug for many patients to take, quite well tolerated, very active, and as I mentioned, it can be combined with daratumumab, it can be combined with carfilzomib, and it can be combineda little less commonly—with cyclophosphamide. So, it does form a good backbone for treatment at first relapse.
Pomalidomide can be safely combined with any of the new novel agents. We do see more neutropenia when it’s combined with daratumumab. That can be up to 40% of patients. And so, with daratumumab, we may often start patients at a lower dose of pomalidomide of 2 mg and perhaps escalate. With carfilzomib, it seems to quite easy to combine with that drug. And again, neutropenia is one of the things we watch for. Patients do need to be on anticoagulant such as aspirin or, if they’re at high risk, full anticoagulation.
Transcript edited for clarity.