Maintenance Therapy Approaches in Multiple Myeloma

Keith Stewart, MBChB: That takes us to the question of consolidation and maintenance, and we just have a few minutes here. Peter, what’s your approach to maintenance today? What drugs, for how long, and low versus high risk. Where are you at with that?

Peter Voorhees, MD: For most patients, lenalidomide is the standard of care. It has a role both in standard-risk patients as well as high-risk patients. The MRC 11 trial showed us that lenalidomide maintenance is active in patients who have the 4;14 translocation as well as deletion 17p. Lenalidomide, and until disease progression for now until a study tells us otherwise, because the CALGB and MRC 11 trial showed a survival advantage post-transplant with the use of lenalidomide maintenance therapy until disease progression. As far as single-agent proteasome inhibitor maintenance, there are no good randomized data supporting that for patients with deletion 17p or the 4;14 translocation. I have gravitated, based on the experience from the Emory [University] group, and now we’ve got my colleague’s S1211 trial looking at RVd [lenalidomide, bortezomib, dexamethasone] induction therapy, followed by prolonged lenalidomide/bortezomib maintenance therapy in high-risk patients with a very respectable median progression-free survival that came out of that study. I have gravitated toward lenalidomide/bortezomib combination maintenance for patients with high-risk disease.

Keith Stewart, MBChB: Just for high-risk, but not for your low-risk patients?

Peter Voorhees, MD: Not for the standard-risk patients.

Keith Stewart, MBChB: Natalie, what’s your approach right now? We accept lenalidomide for everybody?

Natalie S. Callander, MD: I go with Pete, lenalidomide for standard risk, VRd [lenalidomide, bortezomib, dexamethasone] for high risk.

Keith Stewart, MBChB: Including dexamethasone?

Natalie S. Callander, MD: We cut it out quickly. It modulates some [adverse] effects, sometimes some of the cytopenias. But at some starting dose of dexamethasone, but not 40 [mg].

Keith Stewart, MBChB: I know you’re big fans of lenalidomide in Boston. Are you using bortezomib as well?

Nooper Raje, MD: High-risk patients, add bortezomib, change to ixazomib if they have neuropathy.

Keith Stewart, MBChB: Noopur, how long for? There was all this debate that Paul wants to treat forever, and most of us are like, no, 2 or 3 years is probably enough torture.

Nooper Raje, MD: I continue forever unless they have toxicity that precludes them from being on it.

Keith Stewart, MBChB: Tom, could you talk to the role, since you’re doing MRD [minimal residual disease] testing, do you use any consolidation if it’s still positive?

Thomas G. Martin, MD: We don’t use any consolidation. But for the high-risk patients, I’m different. If it’s a high-risk patient who is MRD-positive at 3 months, based on our tests, I’m going KR [carfilzomib, lenalidomide] plus or minus D [dexamethasone] as the maintenance strategy, vis-à-vis the MMRC study. K [carfilzomib] is my preferred maintenance strategy for the high risk. And for standard risk, I am just with lenalidomide.

Keith Stewart, MBChB: What we were doing before I left the Mayo [Clinic], was more aggressive. I was using lenalidomide and bortezomib in almost everybody. More and more are turning to daratumumab if they were MRD-positive, which I find many of my patients are still MRD-positive post-transplant. And I got the notion that daratumumab, even though it’s not really approved yet in this setting, as a consolidation to try and get to MRD negativity was worth a shot. That’s where I was leading. Outside of the United States, of course, many of these things are not feasible at all. And lenalidomide will be the standard of care, as you’ve all said, for everybody, time-limited or forever, and then the use of bortezomib, perhaps, in the higher-risk patients. In Europe, a second transplant is commonly employed. Is anybody doing second autotransplants for their high-risk patients? Natalie, I’ll pick on you because you’re kind of the transplant-avid person here.

Natalie S. Callander, MD: We haven’t, just because I think we were swayed initially by the BMT CTN 0702 [trial]. It released the early data that didn’t show benefit for tandem or consolidation. They updated their data at ASCO [the American Society of Clinical Oncology annual meeting], which is interesting, looking at not just intention to treat, but who received the tandem. They were able to show a benefit for tandem, particularly for high-risk patients. Speaking again to the MRD issue, they also showed that there was a significant benefit for long-term lenalidomide in terms of maintaining MRD negativity. And I thought those were interesting data.

Keith Stewart, MBChB: Anybody doing second transplants?

Peter Voorhees, MD: We’re not at this point. A second look at the StaMINA trial was a bit of cherry-picking, to be honest with you. They are taking the patients who went through the 2 transplants, which are probably the fittest patients. In the absence of randomization of that specific subgroup of patients, you can’t say anything one way or the other. I’ve gravitated away from the 2 transplants.

Nooper Raje, MD: One thing we should highlight here, we keep talking about a second transplant benefiting the high-risk patient population. Remember, including the FORTE trial, including the StaMINA trial, the maintenance did not include a proteasome inhibitor. It was lenalidomide alone. And that’s why it’s hard to put it into practice, because that’s what we typically do for our high-risk patients.

Transcript edited for clairty.