IMiD Sequencing in Multiple Myeloma - Episode 6

Clinical Rationale for Pomalidomide in Myeloma

January 10, 2018

A. Keith Stewart, MB, ChB:Many patients are receiving VRd up-front therapy and eventually becoming resistant to both the proteasome inhibitor and the immune modulator, lenalidomide. At this ASH meeting in 2017, there is a very interesting paper being presented in which pomalidomide has been combined with the alkylating agent cyclophosphamide and with a corticosteroid. In these patients who have had RVd, have had transplant, that 3-drug cocktail with pomalidomide, cyclophosphamide, and a corticosteroid had a very impressive 90% plus response rate. And I think that’s with really quite good tolerability. I think that’s quite an attractive regimen. It’s all oral medications. It’s one that will be well tolerated both by the frail and the fit patient, and I think it’s one that doctors should consider.

One of the recent successes in multiple myeloma has been the POLLUX clinical trial, which looked at daratumumab/lenalidomide/dexamethasone at first or subsequent relapse and had a very positive result. However, many patients in the United States have just progressed on lenalidomide and it’s not a particularly attractive choice of drugs in this situation.

A nice paper presented by Dr. David Siegel at this meeting showed quite clearly that pomalidomide can be combined with daratumumab in this setting of first or third or subsequent relapse with very acceptable toxicity profiles—neutropenia being the one that we have to be careful with—and also was highly efficacious.

The practical implications in some of the new studies we’ve seen at ASH 2017 are of the patients who have received lenalidomide as part of their induction therapy, pomalidomide could be a very attractive option at time of relapse. Pomalidomide we have seen at this meeting can be safely combined with cyclophosphamide. It can safely be combined with daratumumab, and in prior studies from MD Anderson and others, it can be safely combined with Kyprolis, or carfilzomib. So, this combination of different drugs partnered with pomalidomide can be a very successful strategy in first early to relapse.

Despite our best efforts, myeloma is a chronic relapsing disease and patients will often progress beyond this first or second relapse into subsequent relapses. Many patients receive multiple lines of therapy today. Another nice presentation at this meeting has been to look at the role of pomalidomide with low-dose dexamethasone in patients who’ve had at least 2 prior therapies and who have been refractory to lenalidomide as one of the immediate prior or previous treatments that have been received.

This is a real clinical question: lenalidomide-refractory, multiple prior therapies, what useful drugs do we have in that setting? What was shown in this abstract by Dr. Siegel and his colleagues was the use of pomalidomide as a single agent with the addition of dexamethasone can result in a response rate of approximately 30%, even in patients who have recently been refractory to lenalidomide; again, giving us another treatment option in these heavily pretreated patients.

Transcript edited for clarity.