Hematologic Oncology Update, Issue 3, 2016 (Video Program) - Video 22Management of high-risk MM
4:25 minutes.
TRANSCRIPTION:
DR LONIAL: There are a couple of questions about management of high-risk myeloma that continue to be an issue. And the first is, should they get maintenance therapy and what should they get as maintenance therapy? And what we were trying to speak about in that “How I Treat” paper is really the idea that the standard single-agent lenalidomide as maintenance therapy post-auto is not going to be sufficient for patients with high-risk myeloma. Now, there are series that have looked at single-agent bortezomib from the Dutch. And there is a small experience with bortezomib and thalidomide and dexamethasone. But what we were really highlighting in that paper is data from Dr Nooka in our group, published in Leukemia 2 years ago, that looks at RVd as maintenance and consolidation for high-risk patients. And so there are really 2 purposes for that paper. The first is the importance of identifying who the high-risk people are at the time of diagnosis, because if you miss that opportunity, you’re not going to know it until they’ve relapsed really early. The second is, make sure that you’re aggressive with their treatment and that you’re aggressive in their maintenance as well, because if you do that, you can ultimately improve their long-term outcomes. And that was really the crux of the paper. DR LOVE: Now, when you talk about being, quote, aggressive with their treatment, one of the things that I’ve heard from a variety of people, including you, over the years is, it really doesn’t affect that much the up-front induction. DR LONIAL: Correct. DR LOVE: It’s really more in the longer term and maintenance where you see more aggressive therapy and particularly the use of proteasome inhibitors. What about transplant strategies in high-risk patients — for example, tandem transplants? DR LONIAL: Yes. So that’s a good question. There is some retrospective data from the European groups suggesting that high-risk patients who received a tandem transplant had better long-term outcomes than high risk who didn’t receive a tandem transplant. Again, it’s retrospective data. And in our series that I talked about earlier, we didn’t actually do tandem transplant. And our outcomes were as good, if not better, than that retrospective series. One important piece that I think is a caveat, or a carryon along with that message that you raised is I and many others have said, “Two drugs is undertreatment.” And so the concept of len/dex as induction therapy is insufficient. Everybody should get the best induction up front. And what he showed was that if you undertreat a patient at diagnosis, when they relapse they relapse like a high-risk patient. So you’ve almost converted them by undertreating them to a high-risk phenotype. DR LOVE: Another question — and again, from my simple vision of what you all are doing, it seems like this is really a big question related to maintenance. But in terms of defining who gets put into this high-risk category, usually people think more about cytogenetics and FISH. But you also have a table in this paper talking about disease burden, tumor biology, extramedullary disease. Do these factors, again, change your therapy? DR LONIAL: Yes. So they don’t change the therapy on the up-front setting. And I think, as you and I have spoken many times, what you do in the first 4 cycles should be the same and it should be the best. It really changes how you manage the maintenance and the timing of maintenance and the duration of maintenance therapy on the back end. And in addition to FISH and cytogenetics, yes, extramedullary disease at presentation, plasma cell leukemia, these are all important things to keep in mind when you’re thinking about identifying a high-risk patient. The other one that’s becoming a little bit more used nowadays is gene expression profiling, whether it’s one of 2 different companies — you use their high-risk signature. That certainly is reasonable, but it’s probably not the only answer. |