ASH 2017 Conference Coverage
Expert Panel Discussion:
New Data in Smoldering Multiple Myeloma
New Data in Smoldering Multiple Myeloma
World Myeloma Forum Expert Panel members Sagar Lonial, MD; Suzanne Lentzsch, MD, PhD; Ravi Vij, MD, MBA; and Ola Landgren, MD, PhD discuss data presented at ASH 2017 on the management of patients with smoldering myeloma.
The panel discusses two key abstracts presented at ASH 2017.
Abstract 510: Daratumumab Monotherapy for Patients with Intermediate or High-Risk Smoldering Multiple Myeloma (SMM): Centaurus, a Randomized, Open-Label, Multicenter Phase 2 Study. Craig C Hofmeister et al. Blood 130.Suppl 1 (2017): 510.
Full Transcript
Jatin Shah, MD (Moderator): Welcome to World Myeloma Forum, expert panel. It’s a pleasure to have everybody here. We’re going to review some of the key abstracts from ASH 2017. So, before we get started, just as a quick introduction for all of our viewers.
Sagar Lonial, MD: I’m Sagar Lonial from Emory University, Atlanta, GA.
Suzanne Lentzsch, MD, PhD: Suzanne Lentzsch from Columbia University, New York.
Ravi Vij, MD, MBA: Ravi Vij from Washington University in St. Louis.
Ola Landgren, MD, PhD: I’m Ola Landgren from Memorial Sloan-Kettering Cancer Center in New York.
Jatin Shah, MD (Moderator): So, to continue our discussion coming out of ASH 2017 about some of the new data now with smoldering myeloma, two new pieces of data now that came out. One was by Dr. Mateos in smoldering myeloma, the CESAR trial [Abstract 402], which looked at an intensive regiment of KRD transplant, KRD consolidation and RD maintenance for patients with smoldering myeloma in an attempt to cure these patients. And another approach from Dr. Hofmeister [Abstract 510] looking at single agent daratumumab in patients with high-risk smoldering myeloma. Start with you, Ola, on your thoughts on these approaches.
Ola Landgren, MD, PhD: I do think that the Hofmeister study with the daratumumab is very interesting, although it’s a single drug and it’s early. It’s a short duration use of daratumumab of only eight doses. And then there are two long arms that go all the way for three years. So it’s a randomized phase II trial. The patients, there are 41 patients on each arm, so it’s a pretty small study. The primary endpoint was to look for complete response and also for progression-free survival. And the study actually showed there is a progression-free survival between these different strategies. So the two long arms are very different from the short arm. That’s where you have the progression-free survival.
And because it’s an early study, of course you have to pay attention to safety, and in particular for patients with smoldering myeloma. There is not a whole lot of toxicity going on, so this study has already led to the initiation of a phase III trial. And I think that it’s possible that daratumumab could become the first approved drug for the use in smoldering myeloma in the United States. Obviously, we won’t use that single drug. Ultimately, we would like to bundle it, but we have to get drugs approved. So it is an attempt to get the drug approved.
I think that it’s possible that daratumumab could become the first approved drug for the use in smoldering myeloma in the United States.
I think the Mateos study is interesting. It builds on the work that I initiated at the NCI when we used the KRD for eight cycles. So they split it in the middle. So they gave four cycles of KRD and then they did a transplant, and then four more cycles. They had the first presentation of the data here at the meeting at ASH. Very few patients that have done all the cycles. There are 90 patients total enrolled. If you look at the early data that they have here at the meeting, after four cycles and a transplant, both the complete response rate and the MOD rates are very similar to what we presented from the NCI study with eight cycles.
And those few patients who have gone through additional four cycles, they’re also not very different from the eight cycles. And I think the reason for that is because we had actually 100% complete response rate after 8 cycles, so it’s hard to beat 100%. So I think the difference will really be the long-term follow-up. It will be very interesting. Maybe transplant should be done, or maybe it shouldn’t be done. So that will be very interesting.
we had actually 100% complete response rate after 8 cycles
Jatin Shah, MD (Moderator): Sure. Great perspective.
Ravi Vij, MD: I agree. I think that smoldering myeloma remains an area of active research for improving overall prognosis, and both of these have taken somewhat divergent views to try to get there in the context of a clinical trial. I think a transplant being explored is worthwhile in terms of the definition of smoldering myeloma. Obviously, the definitions have changed over the years so it is important to try to do these trials now in an era with revised definitions because our old high-risk smoldering have now become myeloma.
Suzanne Lentzsch, MD, PhD: I want to point out, never the less, despite all the research efforts, smoldering myeloma and treatment of smoldering myeloma should be performed within clinical trials. I do not recommend general kind of, you know, practitioners to treat smoldering myeloma based on those studies. I think we should use the suggested and extended International Myeloma Working Group criteria that included, for instance, free light chain ratio and also MRI lesions. Never the less, I think it shows nicely that we move away from treating patients when they have organ failure, renal failure, anemia, bone lesions, that we move more to an earlier stage at which we are sure that the patient will have a high risk to develop multiple myeloma and that we have the potential maybe to induce long-term remission. I’m not so sure about cure, but it’s a very attractive kind of goal.
Sagar Lonial, MD: Good points. Yeah. I mean I think, to me, response rate and even PFS are not the right answers, because I think the question is can you impact the long-term outcome for these patients? These are very interesting proof of concept studies, but to date, and I will include the Spanish trial in this statement, which is we have no randomized trial showing that true treatment early for smoldering impacts outcome. Because I think the Spanish trial had enough potential problems with it that it doesn’t clearly, definitively say, “You should treat them early.” And I agree, trials, I think, are the only way that one would want to do it.
Suzanne Lentzsch, MD, PhD: To treat patients, yeah.
Jatin Shah, MD (Moderator): So I think really wrapping that up, what’s clear, and I think good points, is that very intriguing data, but we don’t have randomized trials. Current clinical practice should still be observation for these patients with smoldering myeloma or clinical trials for them, and they should not be receiving active systemic therapy outside of a clinical trial setting. But intriguing data, and hopefully with more long-term follow-up and randomized phase III studies that may change in the future, and that’s what we’re trying to head to. Thank you.