Treating High-Risk Multiple Myeloma - Episode 4
Ajai Chari, MD:Whenever we talk about a clinical trial, we should compare the eligibility criteria to the patient sitting in front of us in clinic to see if this patient would have been ineligible and if the risk/benefit profile observed from this study would be applicable to this patient. And the typical features that would make somebody ineligible for clinical trial in myeloma would be organ function. So, renal dysfunction would be a big issue, and up to one-third of myeloma patients can have renal insufficiency. And so, in this particular regimen, the drug that would be most significantly affected by renal dysfunction would be melphalan. Daratumumab, bortezomib, and prednisone can all be given safely in renal dysfunction. It’s really the melphalan that would need to be dose adjusted. Second would be other major comorbidities like cardiac dysfunction, which is often excluded from clinical trials. But one of the limitations thereand there is a lot of talk in ASCO, as well—is that we need to be generalizing our clinical trial eligibility because if we cherry-pick patients, and particularly in myeloma, because our patients are older, older patients are going to have more comorbidities. So, if we become very selective, it limits the generalizability.
In this particular patient, we don’t have any major exclusionary criteria for her not being in the study. And then the other big thing in myeloma clinical trials is probably blood counts. So, patients’ baseline blood countsin particular, neutrophils and platelets—need to meet the eligibility criteria. In this case, this patient would be appropriate for the enrollment in ALCYONE study.
Daratumumab/VMP may be available very soon. The FDA gave it a very favorable and high priority review earlier this year, and we may be hearing in the next few months about the approval. I think the ramification of the approval will be interesting in the United States because, for example, when VMP was approved many years ago, oncologists took that to be able to use bortezomib frontline, but many people weren’t necessarily giving the melphalan with it. And so, in the United States, sometimes we need an approval in a particular line of therapynewly diagnosed, relapsed, relapsed/refractory. Once it’s approved in that line of therapy, you could potentially modify the regimen to suit your patient. So, for example, if daratumumab/VMP were approved in the United States and there’s a patient who had renal dysfunction, a practicing oncologist could say, “I don’t think the melphalan is appropriate for this patient, so I’m going to give a more modified version of the drug, the regimen, for my patient who is sitting here in front of me.”
So, I think we’ll have to see how insurers and payers will deal with the approval in terms of allowing modifications. But I think it’s also very interesting that VRD, which is one of the most widely used regimens for induction in the United States, did not have any phase III supporting data until pretty much about a year ago, and yet it has probably been the regimen of choice for 7, 8 years. So, I think sometimes what happens in oncology is that very exciting combinations and preliminary phase II data are so compelling that physicians change practice. And if the payers are approving it, then those regimens become standard of care well before the pivotal phase III studies approve that particular regimen.
Transcript edited for clarity.