What treatments should be considered at relapse when your myeloma is refractory to Revlimid (lenalidomide)?

What treatments are available for first relapse with lenalidomide refractory disease?

What are some pomalidomide-based combinations to consider?

Well, so I mean, I think our standard here in the U.S., or at least for sure, our standard here at MSK, right, is to treat patients after their initial therapy with maintenance lenalidomide. So maintenance lenalidomide is a lower dose of lenalidomide than we might use in induction. Typically, in our case, it's ten milligrams administered daily, 25 milligrams being the typical full dose of lenalidomide.

So when patients progress on maintenance, you know, one can consider them lenalidomide refractory. And in that situation, agents using Pomalidomide, a cousin of lenalidomide, in combination with one of the anti-CD38 antibodies, either daratumumab or isatuxamab, those can be used. Alternatively, proteasome inhibition with carfilzomib can be used, also in combination with one of the anti-CD38 antibodies.

So currently, those are probably the two combination mechanisms of action that we routinely will use. In some instances, depending on the qualities of the relapse, there are other monoclonal antibodies. So one can use an anti-SLAMF7 antibody, elotuzumab, in combination with full-dose lenalidomide, and sometimes one can see response to that as well.

Now, the patient relapses. Most patients in America will relapse on maintenance lenalidomide. So the question is, are they refractory to lenalidomide? Some people think that's true.

So what are you going to do? What are you going to pick for the relapsed patients?

There is another immunomodulatory drug we can use like pomalidomide, but you have to use combination therapy. So when patients relapse, pomalidomide is one of the three or four drugs you put together to try to eradicate the disease.

What is POMALYST?

So pomalidomide is an IMiD. It's an oral regimen, it's a pill. You take it daily in general for three weeks on, one week off. Some of the side effects that we see can cause people to be kind of tired. It can lower the blood counts, it can cause some numbness and tingling, and in some patients, particularly older patients, if the doses are high, you can get some cognitive changes.

But it's a very effective drug. We have even seen it work along with dexamethasone in REV refractory patients. So it's very effective, and we like to combine it either with daratumumab, you can combine it with isatuxumab and dex—well, everything goes with dex, unfortunately—or carfilzomib and dex.

So those are the best regimens in the early relapse to combine with Pomalidomide. You can also combine it with elotuzumab (elo). Elo-pom-dex is an effective regimen in the relapsed setting.

On April 5th, 2024, the U.S. Food and Drug Administration approved CARVYKTI for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.

To learn more about the drugs mentioned in this video, visit the link in the description.