Novel Concepts in the Management of Multiple Myeloma - Episode 4

Optimal Timing for Transplantation in Myeloma

Transcript:Keith Stewart, MB, ChB: Since you mentioned alkylating agents, let’s use that as an entrée into transplant. We keep trying to get rid of transplant, but we have had no success yet. Saad, there have been some publications recently, from the French in particular, looking at whether or not you can delay or not do transplant at all. Can you summarize for us what those showed?

Saad Z. Usmani, MD: This was the Dana-Farber IFM [Intergroupe Francophone du Myélome] study, but the French portion was accrued quickly and reported out. Dr. Attal just published it in the New England Journal of Medicine. The study compared early versus delayed transplant after RVD [lenalidomide, bortezomib, and dexamethasone] induction, and there was statistically significant and clinically meaningful PFS [progression-free survival] in favor of early transplantation. The overall survival at the follow-up time point, 4 years, was no different, but I think that for most transplant trials, you have to wait out 5, 6, or 7 years to see the overall survival curves separate.

Keith Stewart, MB, ChB: In this trial, MRD [minimal residual disease] was performed. One of the trials we have shows that MRD is an important prognostic factor, right? Do you think it’s changed your practice at all, or was this our standard anyway?

Gareth Morgan, MD, PhD: I think it was confirmatory evidence of the role of autologous stem cell transplant. If you can tolerate it, it should be one of the major tools for newly diagnosed patients.

Sagar Lonial, MD: I think it’s important, though. I agree with you, that I think it does confirm the role, but many in our field say it confirms the exact opposite. They say that you don’t have to do it up front and that you can delay it. Again, I agree with you. I think the important point is that if you look at MRD negativity, two-thirds of the patients who were MRD-negative were in the transplant group.

Gareth Morgan, MD, PhD: Twice as many in the transplanted group as in the non-transplanted group, and they do better.

Sagar Lonial, MD: If you want to roll the dice and presume your patient is going to be in that group at 18 or 24 months, that’s a risk you take.

Saad Z. Usmani, MD: I agree. I think that when you have that conversation with the patient, you want to pick the choice that gives your patient the best chance for getting to a deep remission, MRD-negative, and that’s what you get with early transplant.

Keith Stewart, MB, ChB: The StaMINA trial, which has been presented but not published yet, compared single transplant with a tandem transplant and a single transplant with consolidation with the hypothesis that deeper remission would result in longer progression-free survival. And it didn’t really seem to show that very conclusively.

Gareth Morgan, MD, PhD: It’s just a little bit early for that trial to have reported—about 5 years too early. When it has had adequate follow-up, it will be a really good study, but currently, it’s premature.

Keith Stewart, MB, ChB: Any others want to comment on the StaMINA study? As I recall, there was a slight advantage to tandem transplant, 4 months, and to consolidation, maybe 3 or 4 months—but nothing spectacular.

Sagar Lonial, MD: I think the presumption there is that if 1 transplant is good, than doubling it is better. And I think the reality is, we have better drugs, we do better consolidation, and we do better maintenance now.

Keith Stewart, MB, ChB: Is anybody doing 2 transplants routinely?

Gareth Morgan, MD, PhD: Absolutely. In the last year, the evidence is starting to mount up—the superiority of the German results compared with the Dutch results in the EMN [European Myeloma Network] study.

Keith Stewart, MB, ChB: Plus, it’s done in Europe.

Gareth Morgan, MD, PhD: The EMN consolidation.

Keith Stewart, MB, ChB: Let’s talk about a couple of other abstracts from this meeting, ASCO [American Society of Clinical Oncology] 2017, in Chicago. What about chemotherapy? There’s a German trial, in particular, that looked at the role of doxorubicin liposomal, lenalidomide, and dexamethasone versus bortezomib, lenalidomide, and dexamethasone.

Sagar Lonial, MD: My answer would be, if you use chemotherapy as part of your induction, you probably need a second transplant.

Gareth Morgan, MD, PhD: It’s a good study. The regimens were relevant when the study was designed, but in the combination of Velcade and Revlimid and dexamethasone, which would you rather use with less toxicity?

Keith Stewart, MB, ChB: I think that we have to remember that, outside the United States, giving those 2 drugs together—lenalidomide and bortezomib—is challenging. This offers an alternative, I think.

Gareth Morgan, MD, PhD: I think so.

Saad Z. Usmani, MD: I think so.

Keith Stewart, MB, ChB: You’ve been pretty tough on cyclophosphamide, Dr. Lonial. You never use that anymore in your newly diagnosed patients? Sagar Lonial, MD: Not in newly diagnosed, no.

Keith Stewart, MB, ChB: Does anybody use cyclophosphamide?

Thomas G. Martin, MD: We will use cyclophosphamide, specifically, in patients who have renal failure. Our typical regimen is from the Mayo Clinic, the CyBorD regimen—the cyclophosphamide, bortezomib, and dexamethasone regimen. We will do that until their creatinine clearance or their kidney function improves, and then we’ll actually switch them over to the IMiD [immunomodulatory imide drug]-based therapy.

Keith Stewart, MB, ChB: We do the same. And then there are patients who are sick enough, where you don’t want to wait 2 weeks to give lenalidomide in an outpatient setting. They’re in the hospital, or maybe their insurance isn’t very good, so there’s still a percentage that we still use it too.

Saad Z. Usmani, MD: We do the same.

Ivan M. Borrello, MD: I would say that most of the patients in whom we started in the hospital were started on CyBorD.

Keith Stewart, MB, ChB: If they start in the hospital. All right. There’s another abstract here we want to just quickly talk about—the FORTE trial from Italy. It looked at KRd [carfilzomib, lenalidomide, dexamethasone] versus KCd [carfilzomib, cyclophosphamide, and dexamethasone]. Does anyone want to comment on that? Carfilzomib-cyclophosphamide, or carfilzomib-lenalidomide, up front?

Gareth Morgan, MD, PhD: I’m not fully aware of the results, but I would go with KRd.

Saad Z. Usmani, MD: If I remember correctly, the depth of response was superior. The VGPR [very good partial response] rates were north of 80% on the KRd regimen, whereas they were around 60%, 65% with KCd. I’m not sure about the progression-free survival benefit. It wasn’t reported in the abstract, but it does appear that the IMiD and proteasome inhibitor platform provided better depth of response.

Gareth Morgan, MD, PhD: It comes down to what Keith was talking about—it’s about health technology assessments and the issue of reimbursement in Europe.

Keith Stewart, MB, ChB: My take on this trial was that the cyclophosphamide arm was slightly less efficacious than the lenalidomide arm. But if you’re in a country where you can’t pay for both of those drugs, cyclophosphamide and carfilzomib performed pretty well. It was just marginally less efficacious in terms of response rate, and we don’t have any progression-free survival data yet.

Transcript Edited for Clarity