VIDEO: Multiple myeloma developments for newly diagnosed, relapsed or refractory patients

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I think in myeloma we've been very spoiled in recent years. There are a lot of new, novel types of therapeutic agents coming into the space, particularly in relapsed refractory myeloma. But I think also, recently we've had a lot of developments also in newly diagnosed. And so, last year actually following the phase 2 GRIFFIN study, the randomized phase 3 PERSEUS study was presented at the plenary session at ASH. And this is a really important study. The standard of care induction therapy for newly diagnosed myeloma has been RVd, so lenalidomide (Revlimid, Celgene) with bortezomib (Velcade, Takeda) and dexamethasone (Decadron, Merck). And the phase 2 GRIFFIN study several years ago looked at the additive benefit of daratumumab (Darzalex, Janssen), which is a monoclonal anti-CD38 antibody, to that RVd backbone in induction.

So, four to six cycles of dara-RVd, followed by two cycles of consolidation, and then dara-len maintenance versus len maintenance alone. And what we saw in that study was improved depth of response favoring the quad, as well as the PFS, tran-course PFS benefit. And so, this was confirmed in the randomized phase 3 PERSEUS trial as well. Dara-RVd followed by transplant, and then dara with len maintenance at least for two years. And then there was actually MRD used to risk-stratify for ongoing maintenance. And again, we saw improved depth response favoring the quad over the triplet, which translated to a four-year PFS benefit of around 84% versus 70% or so in the RVd arm. And importantly, at our institution, at Winship Cancer Institute, we've looked at our own patient population that were induced with RVd. We have 1,000 patients historically induced with RVd versus more recently about 325 patients who were induced with daratumumab-RVd.

And I think this is important when we look at clinical trials to also make sure we can validate and translate that clinical trial experience to a real-world population. Because as we all know, clinical trial populations don't always represent what an actual patient population looks like. And so, when we looked at patients in our clinic that were induced with dara-RVd, followed by transplant and what we call risk-stratified maintenance therapy, we again saw that very clear additive benefit of daratumumab. So, I think for us, and what I think should be standard of care, is dara-RVd induction for newly diagnosed patients. There's also been more recent published data looking at quad induction in transplant-ineligible patients, so the MRAs and benefits studies as well as the phase 3 CEPHEUS study, which was just presented at the International Myeloma Society meeting.

I think further discussion really needs to happen about these trials because they are designed to transplant ineligible, but many of the patients in those trials are transplant eligible. At least they would be at our center. So, I think there's probably a more nuanced discussion about what to do and really the role of transplant in some older patient populations. But I think also important data for patients who perhaps are high risk or maybe not transplant-eligible for certain reasons but not frail, and the role potentially of a quad in inducing deep responses in those patients as well. Some of the other novel data or recent data more in the relapse space has to do about CAR T-cell therapy, using CAR T-cell therapy earlier, or using CAR T-cell therapy in different spaces like maintenance or even in newly diagnosed, which is all being under investigation. So, I think a lot more to come.