Transplant and Treatment Decision-Making in Multiple Myeloma
The expert panel discusses factors that influence referral to transplant as well as selecting maintenance and consolidation therapies for patients with multiple myeloma.
Transcript:
Peter Voorhees, MD: When would you typically refer one of your newly diagnosed patients with myeloma who you think might be transplant eligible to the transplant team for consideration?
Amy Soni, MD: Yeah, I think in that cycle 2 or 3 of induction therapy ballpark, after we have diagnostic studies and I see that they’ve tolerated at least a cycle pretty well, just to get them on the radar and start planning transplant if that’s the way this is headed.
Peter Voorhees, MD: Yeah. I would completely agree with that. And what I typically tell oncologists both within the LCI [Levine Cancer Institute] system as well as outside of LCI is, the sooner you refer to us, the better, for a number of different reasons. One, with cellular therapies increasing in volume in general, including CAR T-cell therapy, which we’ll be talking about a little bit later in the program, the capacity for our apheresis teams, for our cellular processing lab teams, is becoming increasingly burdened. So, the earlier you get your patients in, the sooner that we can get their foot in the door and scheduled with potential dates for stem cell mobilization and collection and transplant itself.
The other thing that I think that’s important to recognize, we’ve talked about the increasing utilization of quadruplets over triplets in these patients. And there is a signal for impairment of stem cell mobilization and collection for those patients that get a CD38 antibody and lenalidomide as part of their initial induction therapy. And the longer that they’re on those therapies, the harder it is to collect stem cells. The earlier you get them in, the better off they do. We’ve got good data that you can collect stem cells successfully for 2 transplants if they’ve had 12 weeks of induction therapy with a CD38 antibody and lenalidomide, even out to 18 weeks based on the GMMG-HD7 study [NCT03617731], which looked at isatuximab with RVd [lenalidomide, bortezomib, and dexamethasone] in transplant-eligible patients. But we have no data beyond that. So, I typically advise people, get them in soon so we can get them collected after 12 to 18 weeks of initial induction therapy.
Let’s go on to the consolidation and the maintenance settings. Reed, are there any specific circumstances where you might provide consolidation therapy for a patient after they’ve recovered from a stem cell transplant?
Reed Friend, MD: I think considering for high-risk patients or patients who have not achieved the optimal response that you’re looking for posttransplant, hoping to consolidate them before moving them on to maintenance.
Peter Voorhees, MD: Okay. And if they were treated with dara[tumumab]-RVd in induction therapy and have responded nicely to it, get transplanted, but they’re still MRD positive, for example, perhaps not quite in a CR [complete response] after recovery from transplant, what consolidation would you use? Would you go to the same regimen that you used during induction, or would you use something different?
Reed Friend, MD: I’d like to use the same thing that we had from the beginning. Minimize exposure to other drugs and leave other options for later on, especially if they’ve been responding.
Peter Voorhees, MD: Right. And, you know, in the GRIFFIN study [NCT02874742], again, we did use 2 cycles of posttransplant consolidation uniformly across all patients. So, they got a total of 6 cycles of Dara-RVd before and after transplant. So, let’s go on and talk briefly about maintenance therapy. What would be your go-to regimen as far as maintenance therapy in most of your patients who have recovered from transplant?
Amy Soni, MD: I think in the majority it’s still just Revlimid.
Peter Voorhees, MD: Yes. I would agree with that. And this question comes up now, should we be adding daratumumab into the lenalidomide maintenance therapy? Because that’s what we did in the GRIFFIN trial. And I think that the jury is still out on that one. You know, obviously, we produced great results in the GRIFFIN study. But there are also data from a phase 3 study called CASSIOPEIA [NCT02541383], where patients got dara, bortezomib, thalidomide, and dexamethasone before and after transplant. But there was a second randomization to no maintenance or daratumumab maintenance. And interestingly, and not surprisingly, daratumumab maintenance improved progression-free survival in that particular study. But it was all fueled by the inferior progression-free survival for those who got bortezomib, thalidomide, and dexamethasone followed by no maintenance therapy. So, if you got daratumumab with your VTD, you didn’t seem to benefit from a PFS perspective with daratumumab maintenance therapy.
Going back to this GMMG-HD7 study from Germany, which is looking at isatuximab with RVd in the transplant scenario, they’re doing a second randomization to either lenalidomide alone or isatuximab and lenalidomide. And that’s going to answer the question, you know, whether there’s a role for the CD38 antibody in addition to the lenalidomide in the maintenance setting in that group of patients. Kwabena, is there a group of patients where you might consider using lenalidomide with, for example, a proteasome inhibitor?
Kwabena Osei-Boateng, MD: [Patients with] high-risk cytogenetics.
Peter Voorhees, MD: I would agree with that. And we actually have randomized data to support that at this point, too. The FORTE trial [NCT02203643] was a randomized, phase 2 study that looked at a number of different questions. But one of the questions that they addressed was lenalidomide with or without carfilzomib as maintenance therapy for all patients. And not surprisingly, there was a PFS advantage for those who got the 2-drug maintenance therapy. But when you broke it down by cytogenetic risk, both standard-risk, as well as high-risk patients, seemed to benefit from the combination of lenalidomide and carfilzomib. So, I think you’ve got pretty strong evidence these days to support using lenalidomide with a proteasome inhibitor in that group of patients.
Transcript is AI-generated and edited for clarity and readability.
