Shared insight on the optimal selection of induction therapy for patients with high-risk transplant-eligible newly diagnosed multiple myeloma.
Alfred Garfall, MD:You mentioned the MAIA study. This patient was in his 70s. He is healthy and was declared to be a transplant candidate, but he’s in that borderline age where patients sometimes elect not to go to transplant or have other medical conditions. Sandra, can you talk about MAIA and how it might apply to somebody in this situation?
Sandra Susanibar-Adaniya, MD: The MAIA study was a phase 3 randomized clinical trial that studied the addition of daratumumab to the standard of care for people who weren’t eligible for transplant. In addition to the backbone of Revlimid-dexamethasone, you add daratumumab. The results have been very exciting. In close to 5 years of follow-up, the median progression-free survival has not been reached for the subgroup of patients who received daratumumab vs 36 months. That was shown in the Revlimid ... group. That’s very similar to what was shown in the small phase 2 VRd [bortezomib, lenalidomide, dexamethasone]–lite study. For people who are borderline candidates for transplant, these data allow us to have a deep discussion—maybe not in 1 visit but in a couple of visits—about what the patients prefer. We have many options for these patients, but starting with daratumumab-Revlimid-dexamethasone is an excellent option.
Alfred Garfall, MD:To your point, Ed, about not necessarily deciding about transplant in the first visit, we have these regimens that are all safe and highly effective: daratumumab–VRd [bortezomib, lenalidomide, dexamethasone], VRd [bortezomib, lenalidomide, dexamethasone], and DRd [daratumumab, lenalidomide, dexamethasone]. I feel comfortable using them with proper monitoring in transplant-eligible and -ineligible patients and certainly in these borderline cases. Are any of those a wrong answer for somebody in this scenario?
Dan Vogl, MD: It’s important to start from what we think our standard advice would be. Our standard advice evolved from studies that showed the efficacy of lenalidomide-based induction regimens over previous options like thalidomide, pulse dexamethasone, or chemotherapy induction. The seminal study was SWOG-S0777, which compared a bortezomib-lenalidomide combination with lenalidomide-dexamethasone and showed an overall survival benefit. In our practices at the University of Pennsylvania, the standard induction regimen for both transplant-eligible and transplant-ineligible patients is the VRd [bortezomib, lenalidomide, dexamethasone] regimen. There are clinical situations in which we might want to add daratumumab, avoid bortezomib, and go with a regimen that has less treatment toxicity, especially less peripheral neuropathy, like the DRd [daratumumab, lenalidomide, dexamethasone] regimen. There should be a reason that draws us away from that standard. Although we have exciting preliminary data on response rates and duration of response progression-free survival, we don’t have any studies that show an overall survival advantage for a different regimen compared with the combination of bortezomib, lenalidomide, and dexamethasone. That’s why it remains the default choice. In individual clinical situations, there may be a rationale for using something different.
Alfred Garfall, MD:We have overall survival data from the MAIA study of DRd [daratumumab, lenalidomide, dexamethasone] vs Rd [lenalidomide, dexamethasone], but there hasn’t been a randomized phase 3 comparison to my knowledge of VRd [daratumumab, lenalidomide, dexamethasone] vs daratumumab–Rd [lenalidomide, dexamethasone] .
Edward Stadtmauer, MD: I agree with all these comments. The major point I want to make is that I’d love to do away with the transplant-eligible vs transplant-ineligible way of categorizing patients. What we’re really talking about is old and frail vs young and healthy. We’ve been saying that age isn’t necessarily the most important criterion. Performance status and the whole study of frailty in blood cancers—and in cancers in general—have a major effort. It’s important to think of those criteria and to use them as a moving target. Patients will be frail at the beginning and then become better and better. Once a patient has been put into remission, that’s the time to decide the best consolidation of that remission to maintain long-term healthy remissions. It’s wonderful that we have high-dose melphalan and all the other therapies in our list of things.
Transcript edited for clarity.