Role of Maintenance Therapy and Key Takeaways in Transplant-Eligible NDMM


Before closing out their discussion on transplant-eligible NDMM, expert panelists consider the role of maintenance therapy following transplant.


Ajai Chari, MD: We’ve spent a little time [discussing this, and] it sounds like everybody’s doing 4 to 6 cycles and like we’ve all drank the transplant Kool-Aid. But there was an interesting study about what to do post transplant. This also gets to your point about the ATLAS study [NCT02659293], which [is a] randomized study of carfilzomib [lenalidomide] vs [lenalidomide]. It was 8 cycles of KRd [carfilzomib, lenalidomide, dexamethasone] or KR [carfilzomib, lenalidomide] vs [lenalidomide] alone. This was presented by the Polish Chicago Group and it showed a significant benefit to KR maintenance. [It was] similar to the FORTE study [NCT02203643], which we had heard about from [the American Society of Hematology]. I’m curious what [you] think about dual maintenance therapy. Were you impressed by the data?

Rafael Fonseca, MD: The data [are] impressive. I think it’s agnostic to the drug. I’m thinking it builds on the MRD [minimal residual disease]. If you have residual disease, now I say more of good treatment is good until we can eradicate whatever’s left behind. We see this through FORTE and through an [electrophoretic mobility of cell nuclei] study. I know there’s the exception of stamina, but in general, we’re seeing more of good treatment—whether that’s [daratumumab], carfilzomib, etc—[which] results in better outcomes. Now people are going to say that’s a foregone conclusion, [which is] true, but that’s why we [must] continue to measure the depth of these responses. Because part of the reason is once your MRD is 10-6, there are 2 possibilities: you’re less than 10-6, but there is disease left behind, or there’s a real possibility in some patients [that] there are no cells left behind. And we will never be able to prove that. You can’t prove a negative. That is the biggest question we have.

Cristina Gasparetto, MD: I agree.

Ajai Chari, MD: Anybody else on posttransplant? Are you changing your practice with more monotherapy maintenance?

Cristina Gasparetto, MD: I’ve always used double therapy for high-risk [patients] for ages. With standard risk, I’m content with single agents. I always felt uncomfortable, so I’m not surprised to see some of these data with double PI [proliferative index].I wish when we designed studies in maintenance, the maintenance could also differentiate between high risk and standard risk. We need to have more genomic differentiation and choices, because we can’t treat all our patients the same way.

Ajai Chari, MD: Another point to make with these double maintenance therapies is, again, moving from clinical trial to the real world.

Cristina Gasparetto, MD: Exactly.

Ajai Chari, MD: It’s one thing to do twice-weekly carfilzomib in a clinical trial, but is that happening in the real world in the era of COVID-19?

Cristina Gasparetto, MD: It’s not going to happen.

Ajai Chari, MD: We need these studies. To conclude this exciting discussion, what are our take-home messages? I think this slide tries to summarize some of the messages. One important question is the role of transplant. [With] this slide—for the interest of simplicity—we’ll focus on the PFS [progression-free survival], which is shown in the bar graphs, and then the studies or titles are there. IFMO-9, FORTE, and DETERMINATION [NCT01208662] are on the very right and share the question of whether to transplant and what the role [is]. They’re all showing the transplant has a value add of [approximately] 40% improvement in PFS, [which is] shown at the hazard ratio on the top.

Then the other studies are asking the question of 4 vs 3 drugs, so you can either do DVTd [daratumumab, bortezomib, thalidomide, dexamethasone], DVRd [daratumumab, bortezomib, lenalidomide, dexamethasone], DKRd [daratumumab carfilzomib, lenalidomide, dexamethasone], or ISA-VRd [isatuximab, bortezomib, lenalidomide, dexamethasone]. Again, we’re seeing a consistent message for those that have a more mature follow-up with PFS benefit. Interestingly, CASSIOPEIA [NCT02541383] is also trending toward [overall survival] benefit, [and the] GRIFFIN trial [NCT02874742] is a randomized phase 2, so we’ll have to stay tuned.

This is all exciting, and there’s just a wealth of evidence-based medicine [that is] fortunately helping us guide. It seems like the panel agreed on the role of transplant. It seems like everybody’s doing [quadruplet therapy]. There may be slight nuances in which PI or which CD38, but [quadruplet therapy], transplant, [lenalidomide] maintenance, [and] perhaps double maintenance for high risk. So at least we agreed on something, which is an accomplishment.

Krina Patel, MD: This might be the only time, but–

Ajai Chari, MD: This is a great discussion. Thank you.

Transcript edited for clarity.

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