A New Wave of Progress in The Treatment of Multiple Myeloma: Translating Evidence to Clinical Practice - Episode 5
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?
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.