Improving Maintenance Therapy for Myeloma

Keith Stewart, MD, ChB, MBA: Can we do better maintenance, Joe?

Joseph Mikhael, MD: Yeah. This is 1 of the greatest areas that we’ve learned more about in the last few months. With further updates in the GRIFFIN study, which initially was D-VRd [daratumumab, bortezomib, lenalidomide, dexamethasone] vs VRd [bortezomib, lenalidomide, dexamethasone]. We all talked about the induction part, but we didn’t talk much about the maintenance part—which patients who had D-VRd [daratumumab, bortezomib, lenalidomide, dexamethasone] stayed on DR [daratumumab, lenalidomide] for up to 2 years, then the D daratumumab was dropped. If they remained in remission, then they continued lenalidomide vs lenalidomide alone.

The FORTE study that Sagar and others have mentioned, was a little different from KRd [carfilzomib, lenalidomide, dexamethasone] plus or minus transplant, and then a second randomization comparing KR [carfilzomib, lenalidomide] vs R [lenalidomide]. That was updated recently at ASCO [American Society of Clinical Oncology Annual Meeting]. What we’re seeing, Keith, is that we can do better than lenalidomide maintenance alone, in the higher-risk patients in particular. The evidence for KR [carfilzomib, lenalidomide], in the highest-risk patients, seems to be the strongest. In the other study I mentioned—in which the daratumumab maintenance maybe wasn’t necessary—if you had daratumumab in induction, then there still needs to be a bit of maturity. But the bottom line, at the end of it, is that we’re going to be doing more than lenalidomide alone. We’ve already been doing this for high-risk patients—adding something else, such as bortezomib. Now we have 2 more options: carfilzomib and daratumumab. Maybe, even in standard risk, we’ll be doing more than lenalidomide alone to keep that remission longer. Sagar’s comment about sustained MRD [minimal residual disease] negativity is critical.

Keith Stewart, MD, ChB, MBA: We’re going to come to that. I want to focus in on this first issue. Of these medications, if I’m a community oncologist watching this—which is the majority of our audience—I’m thinking that nothing is FDA approved, except lenalidomide. That’s correct, right? Nina, what are you doing as maintenance in your post-transplant patients and standard high-risk patients?

Nina Shah, MD: For standard risk, as it was called forever, the patient is taking the Revlimid [lenalidomide] because we know that the longer the patient gets lenalidomide, they do better. Multiple different analyses have shown this, and the higher dose that they get is better—but it’s sometimes difficult to tolerate more than 10 mg. For the high-risk patients, we also use proteasome inhibitor [PI] combination therapy because what we’re doing isn’t enough with standard lenalidomide therapy. I agree with you, Keith, that we haven’t had anything else come on board telling us that we should do anything different—as far as standard risk goes—aside from lenalidomide maintenance therapy. It is, as I call it, the Tom Brady of maintenance. It always wins.

Keith Stewart, MD, ChB, MBA: When you say you’re using a proteasome inhibitor for high-risk patients, which 1 are you using? For how long?

Nina Shah, MD: It depends. A lot of patients will come to us from a community oncologist who has already started therapy. If they already got VRd [bortezomib, lenalidomide, dexamethasone] up front, then I emulate it—with what the Emory University School of Medicine group has done—and give extended VRd [bortezomib, lenalidomide, dexamethasone] after transplant. But if they’ve gotten KRd [carfilzomib, lenalidomide, dexamethasone] up front, then I emulate what The University of Chicago Pritzker School of Medicine group does—a modification for another 4, and then 10 cycles. It depends on where the patient started before he or she came to me.

Keith Stewart, MD, ChB, MBA: Is anybody using ixazomib [Ninlaro] or carfilzomib [Kyprolis] in the maintenance setting at this point? You’re nodding. Yes, Sagar?

Sagar Lonial, MD, FACP: Not as a single agent. We may use ixazomib or carfilzomib in the 414 subset, where we tend to go with a PI in the maintenance setting. But with our switch to KRd for high-risk induction, we’ve switched our maintenance to KRd [carfilzomib, lenalidomide, dexamethasone] for 3 years, and then go to single-agent lenalidomide after that. We’ve made the switch from bortezomib maintenance and consolidation to carfilzomib in that situation.

Keith Stewart, MD, ChB, MBA: Three years of carfilzomib. Wow, that’s brave.

Sagar Lonial, MD, FACP: But you’re the 1 who loves carfilzomib. I thought you’d be excited about it.

Keith Stewart, MD, ChB, MBA: Well, how frequently are you giving it?

Sagar Lonial, MD, FACP: We give it once a week: 3 weeks on, 1 week off. Just like what we did with our VRd [bortezomib, lenalidomide, dexamethasone]: once a week, 3 weeks on, 1 week off.

Keith Stewart, MD, ChB, MBA: Would you consider replacing carfilzomib with daratumumab and moving forward? It’s easier to take, and probably as effective.

Sagar Lonial, MD, FACP: It is. If you’re talking about the high-risk cohort, then I’m going to need to see some convincing data. For the standard risk—you mentioned the RVd [lenalidomide, bortezomib, dexamethasone] 1000 series earlier—the median PFS [progression-free survival] for lenalidomide alone, after RVd [lenalidomide, bortezomib, dexamethasone] induction and transplant, is 77 months. So you’ve got to be pretty good, or say that we’re going to shorten the duration of maintenance by giving a doublet as consolidation and maintenance to the standard-risk patients.

Transcript Edited for Clarity