The Evolving Treatment Landscape of Transplant-Eligible Newly Diagnosed Multiple Myeloma

Opening discussion on the management of transplant-eligible newly diagnosed multiple myeloma, expert panelists consider the role of quadruplet therapy and transplant in this setting.


Sagar Lonial, MD: Hello, and welcome to this Cancer Network Around the Practice® program titled, “Expert Perspectives on the Role of Traditional Versus Emerging Therapies in Multiple Myeloma.” I’m Sagar Lonial, chief medical officer of the Winship Cancer Institute of Emory University and professor and chair in the Department of Hematology and Medical Oncology at the Emory University School of Medicine [in Atlanta, Georgia]. I’m joined today by a panel of experts in multiple myeloma. I would like to welcome my esteemed fellow panelists to introduce themselves.

Timothy Schmidt, MD: I’m Tim Schmidt from the University of Wisconsin.

Sandy Wong, MD: Hi, I’m Sandy Wong from the University of California, San Francisco.

Caitlin Costello, MD: Hi, I’m Caitlin Costello. I’m an associate clinical professor of medicine at the University of California, San Diego.

Samuel M. Rubinstein, MD: I’m Sam Rubinstein, assistant professor of medicine at the University of North Carolina, Chapel Hill.

Sagar Lonial, MD: Thank you all for joining us today. We’ve got a lot of information to cover in the next hour or so. Let’s get started with the transplant-eligible patient population. Dr Costello, do you want to get us started?

Caitlin Costello, MD: Sure. What an exciting time it’s been in multiple myeloma. We’ve seen such an explosion of new medicines available for the relapse-refractory period, but I would argue that what we’ve been seeing happening for newly diagnosed myeloma has been equally as exciting. We’ve seen such a significant evolution of the treatment of these patients in the last 5-plus years, where we’ve seen that change from doublets to triplets to wondering now if 3 is better than 2 or is 4 better than 3. Finally, we have some good long-term data looking at the quadruplets, as an example. The historical context of breaking it up [into] transplant eligible versus transplant ineligible is also undergoing quite an evolution too, where maybe now we’re looking at frail or fit patients to help us make some of those decisions. If we’re approaching our patient who is fit, for example, we now are in a position where we’re [asking if we should] be giving quadruplets to everybody. There’s nice long-term data that we’ve seen this summer of the quadruplets from the GRIFFIN study [NCT02874742] that is looking at the addition of CD38 monoclonal antibodies to the triplet…that we’ve so commonly become comfortable with: lenalidomide, bortezomib, and dexamethasone. That long-term follow-up, now 4-plus years, is really hard to ignore. [We’re] seeing that these patients who are transplant eligible, fit, [and] good for transplant are the patients [from whom] we should be getting deep and durable responses. It met its primary end point of looking at stringent complete responses. We see very deep responses with MRD [minimal residual disease] negativity rates that are high, and progression-free survival benefit is just the same. I think the example of the fit patient now is probably looking at quadruplet therapy versus that new standard of care. I know someone else is going to touch on unfit, so I’ll leave that and not steal someone’s thunder.

Sagar Lonial, MD: Let’s talk a little bit about that. Quads [quadruplets] for everybody. Is that what everybody’s doing?

Samuel M. Rubinstein, MD: Yes. At our center, we offer all patients, regardless of risk stratification, who are eligible for transplant, a frontline quad. Our standard is to use daratumumab, lenalidomide, bortezomib, and dexamethasone.

Timothy Schmidt, MD: I will say we have been one of the centers that had been doing triplets for a long time, even after some of the data from GRIFFIN had come out. Just looking for some more of that longer-term data as Caitlin had mentioned. Also with the GRIFFIN study, I think that there was a little bit of a caveat in terms of the continuous daratumumab being all in the same arm, and really whether that was leading to the longer PFS [progression-free survival] seen in that arm, not knowing whether it was the induction or the maintenance setting. I think as we’ve seen data come out from all these studies looking at CD38, in addition to the PI [proteasome inhibitors] and IMiD [immunomodulatory drugs] backbone in newly diagnosed myeloma, what we’re really seeing is consistent benefit in terms of response, depth of response, and MRD negativity. Progression-free survival is starting to emerge. Also, I think…looking at the quality of life measures in the GRIFFIN study where pain scores improved more rapidly and things like that, this is something that we need to be doing for everybody who’s a candidate for more intensive therapy.

Sagar Lonial, MD: I think you bring up a really important point. If we’re going to use the GRIFFIN trial as a model, do we feel like we have sufficient data to say not only are we going to use CD38 up front, but we’re going to use it in the maintenance and consolidation phase. I’m sure you are familiar with the CASSIOPEIA data that said it doesn’t matter when you get it, as long as you get it. Certainly, one thought we have at our center is, we give it up front. This way we don’t necessarily have to give it on the back [end], but that’s sort of picking and choosing data.

Sandy Wong, MD: On top of that, we’re one of the institutions that doesn’t use quads for everybody in the up-front setting who are transplant eligible. Our rationale is that the GRIFFIN data looks wonderful and impressive. [But it] is still a phase 2 study. Furthermore, when it reads out it will probably be a positive study. However, if you look at the people who are high risk in that study, they were not well represented. It’s really a study for standard-risk patients. For us, for standard-risk patients [are those who] get the dara-RVd [daratumumab-lenalidomide, bortezomib, dexamethasone], but I think for high-risk patients, we have to be doing something more because we know that those patients are not going to do well. I’m just not sure that data is there for the dara-RVd [for high risk patients]. However, we have FORTE [NCT02203643]. I give major kudos to them because they really enrolled a lot of high-risk patients, and they use KRd [carfilzomib, lenalidomide plus dexamethasone] for induction. We actually use KRd for high-risk patients, whereas for standard-risk patients, I totally agree with you, dara-RVd is the way to go.

Samuel M. Rubinstein, MD: I think you make a key point, which is that a lot of time people who are tenuously adopting the quad think of it more as an option for patients with high-risk myeloma, but the vast majority of the patients on the GRIFFIN trial had standard-risk disease. To the extent you can slice and dice subgroups, it seems like they derive relatively more benefit than the folks with high-risk disease. I think of the rationale as being stronger for patients with standard risk, newly diagnosed myeloma than for high risk actually.

Sandy Wong, MD: I completely agree with you. If you think about what happens after they get the DARA-RVd, they may get the DARA-Revlimid [lenalidomide], they may get Revlimid; selecting people who are going to be standard risk. I’m not surprised that the representation of standard risk is so strong because it’s the way that the trial is set up. I completely agree with you.

Transcript edited for clarity.

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