An overview of doublet and triplet regimens used as first-line therapy for patients with newly diagnosed multiple myeloma who are eligible for transplant.
Saad Z. Usmani, MD: Let’s go to the next question, which is pertinent to how we approach induction treatment for patients of multiple myeloma. We have 7 choices of first-line induction treatment. Among ourselves, we have been debating about some of these questions, so this will be great. For this patient, your choices of treatment are: VRd [bortezomib, lenalidomide, dexamethasone] as induction, daratumumab, RVd [lenalidomide, bortezomib, dexamethasone] or VRd [bortezomib, lenalidomide, dexamethasone], KRd [carfilzomib, lenalidomide, dexamethasone], and CyBorD [cyclophosphamide, bortezomib, dexamethasone]. There may be other modifications of these induction regimens. What are your thoughts on picking 1 of these choices to treat patients, triplet vs quadruplet regimens? We can start with Sham first.
Sham Mailankody, MD: First, all the choices you mentioned are treatments for triplet regimens or quadruplet regimens, and that’s important. There should be very few patients, if any, treated with doublets in modern times. Obviously, there are patients in our clinic who may need doublet treatment for various reasons, but the default position should be to go with a triplet or a quadruplet regimen. All the choices you mentioned are quite reasonable.
There are obviously ongoing studies and some uncertainties about which triplet regimen to choose and whether to add a quadruplet regimen. In general, I’ll definitely go with a triplet regimen at a minimum. For patients who have aggressive disease presentation or high-risk cytogenetics, there may be more of an inclination to go with a quadruplet—for instance, with updated results from GRIFFIN. We’re recognizing more that while we’ve made significant progress for patients with high-risk myeloma, we continue to need new approaches and innovations in how we treat them. It would be reasonable to consider a quadruplet regimen like daratumumab [Darzalex] and RVd [lenalidomide, bortezomib, dexamethasone], based on the GRIFFIN study.
This patient has standard-risk cytogenetics and is a young person. Any of these choices would be reasonable. He has a creatinine clearance of 45 mg/dL, which would not preclude him from getting lenalidomide [Revlimid], but that may be 1 reason why some physicians would consider CyBorD [cyclophosphamide, bortezomib, dexamethasone] for a cycle or 2 until the renal function stabilizes, but any of the mentioned choices would be quite reasonable.
Saad Z. Usmani, MD: What do you think, Dr Shah and Dr Korde?
Neha Korde, MD: For my standard-risk patients who are young, because of the ENDURANCE study, I’ll often choose KRd [carfilzomib, lenalidomide, dexamethasone] if I have a clear understanding of where their cardiac history is or is not. In this patient, if he has a relatively benign cardiac history, I’ll choose carfilzomib [Karprolis] up front. For high-risk patients, it’s a little less clear. It’s a bit shaky in terms of where the data really sit. In my older standard-risk patients, I tend to go with RVd [lenalidomide, bortezomib, dexamethasone] because it’s fairly tolerable. But overall, as Dr Mailankody said, a lot of the choices listed are possible for this patient.
Sham Mailankody, MD: I was going to add 1 more thing. When you use Velcade [bortezomib], it’s obviously very important, as everybody probably knows, to use it subcutaneously. It may be potentially important for most patients to do this treatment weekly rather than twice weekly, which probably lowers the risk of neuropathy—the big concern with the drug.
Saad Z. Usmani, MD: I agree. The days when we would be dosingVelcade twice weekly are gone. Going for the once-weekly dose—you can play around with the dose a little as well, to make it tolerable—should be chosen from the get-go. What do you think, Dr Shah?
Urvi Shah, MD: I tend to agree with what everyone has said, but some things call for a discussion with the patient about the toxicities around these drugs. Patients sometimes have very strong preferences about carfilzomib, which has a slight increased cardiotoxicity, vs bortezomib, which has neuropathy. I tend to bring up the basics of the data. The ENDURANCE study showed no difference between VRd [bortezomib, lenalidomide, dexamethasone] and KRd [carfilzomib, lenalidomide, dexamethasone], but there may be some phase 2 studies that suggest that this is combination is good. It’s important to see what the patient is leaning toward. I tend to prefer Velcade [bortezomib] options, given the ENDURANCE trial results, the cost, and also because it’s IV [intravenous] vs subcutaneous. I find that having to come in weekly for an IV therapy vs just having a shot is a significant quality-of-life benefit unless neuropathy is an issue.
Saad Z. Usmani, MD: These are very important points. To talk about this, because you mentioned the ENDURANCE trial—the large, randomized phase 3 study that looked at VRd [bortezomib, lenalidomide, dexamethasone] vs KRd [carfilzomib, lenalidomide, dexamethasone] as part of induction therapy, showing no difference in terms of PFS [progression-free survival] benefit, with different safety profiles. My take was that both regimens are comparable. You just have to find the right profile for the right patient.
Sham Mailankody, MD: Comorbidities drive it to a larger degree as well. Somebody with diabetes, for instance, or a higher risk of neuropathy might steer clear. For somebody with a mild to moderate degree of cardiac history, maybe you would want to go with Velcade [bortezomib]. And patient preference—I had a musician who didn’t want any grade neuropathy; therefore, it made sense to do carfilzomib as his initial choice. Many times patients’ stories, or what patients tell us, will influence what regimens we use, but we can feel comfortable that both treatments are equally effective, at a minimum, based on the ENDURANCE study. They have somewhat different safety profiles, so that may play a role, but the highlight is triple regimen, at least, for most patients. Then consider a quadruplet regimen in the coming years as well while more data emerge from GRIFFIN and other studies.
Transcript edited for clarity.