Treatment Regimens for Frail Patients with Transplant-Ineligible NDMM
Rafael Fonseca, MD, and Krina Patel, MD, discuss the standard treatment approaches for frail or elderly patients with transplant-ineligible multiple myeloma.
Rafael Fonseca, MD: Dr Krishnan, here’s another hard question. Can you compare the MAIA trial with SWOG S0777?
Amrita Krishnan, MD: Sure. I learned I’ve been pronouncing ALCYONE wrong for years. Thank you for that.
Rafael Fonseca, MD: Don’t look at me as the pronunciation standard.
Amrita Krishnan, MD: It speaks to the era when we had the prescription pad, as you mentioned. Those were the golden eras. There was no Epic [electronic health record system], you’d just scribble 3 lines, you had a prescription pad. But obviously, in terms of therapy options, we’re in the golden era now, and hopefully even more so. I look at SWOG S0777 as a past era. Because first of all, Velcade [bortezomib] was given the traditional way twice a week, which we rarely do IV [intravenously]. In terms of toxicity, you’ve already stacked the odds that you’re going to have much more toxicity from that. The median PFS [progression-free survival] was 41 months in that trial, which was pretty astounding when that came out. But to your point, our standards have gotten a lot higher now. I certainly like daratumumab-Rd [lenalidomide, dexamethasone] for my transplant-ineligible patients as well in terms of toxicity. Not getting neuropathy and quality of life are so important, especially in older patients.
The other thing I should mention is the whole idea of frailty scoring. We led a couple of trials in our institution using an iPad frailty score. Our eyeball test isn’t the greatest. You’re always surprised when someone has been very functional and working but you start them with therapy and things fall apart. To your point, [it’s important to] have a more true assessment. I’ve tried some of those tests, such as getting out of a chair unassisted. I challenge everyone to do that now. It isn’t that easy.
Caitlin Costello, MD: Yes, it’s hard.
Rafael Fonseca, MD: Absolutely. Let’s explain a little about frailty. Dr Patel, there’s a subset analysis that was done for MAIA. That made me scratch my head. Because if you asked me a year ago, I’d say, “There’s definitely a role for doublets in those who are frail,” but what did we see in that subset analysis?
Krina Patel, MD: Basically, they looked at all the patients as fit, intermediate, or frail based on the tests that we do. One day, I hope we can all do them all the time in the clinic. We need better access to be able to do those. They put the fit and intermediate patients together. Then they put the frail patients separately to look at outcomes. If you compare the frail patients with the fit and intermediate, they potentially had a slightly lower PFS. But within the group of the frail patients, they still did better with the triplet than the doublet. They haven’t reached progression-free survival yet in the triplet arm. In the doublet arm with Rd, it’s about 30.4 months. They actually did better. They’re responding better for longer. The toxicities were really similar. There wasn’t much more neutropenia or infections or anything. They were able to stay on therapy.
In the last 8 years that I’ve been [part of the] faculty, I’ve never used a doublet, because these studies came out as I became faculty. I always choose a triplet. Very rarely have I ever used a doublet. The only reason I’d ever choose a doublet is in a patient who couldn’t get a CD38 because of bad lung disease or another reason.
Rafael Fonseca, MD: Let me ask you a follow-up question to that. We now talk about quadruplets in the front line. [Let’s say] I’m talking to a new audience. We’re talking about quadruplets, and they say, “Yes, you convinced us of that. But why don’t you do that for older patients? Why don’t you do that for patients with relapsed and refractory myeloma?” There are almost no clinical trial data for quadruplets there. Do we undertreat older patients? Do they need a PI [proteasome inhibitor]? That’s a very tough question. Are we OK as we are with using a triplet like daratumumab-Rd?
Krina Patel, MD: That’s a great question. Because it’s undertreating vs overtreating. I try to get some of my patients who have high-risk disease, plasma cell leukemia, through a quadruplet because I know this is my 1 chance to get them the therapy they need to hopefully have a response. But other than that, we’ve seen such great data with the triplets that are we now just going to add more adverse effects and toxicity? Are we going to have any actual benefit to what DRd [daratumumab, lenalidomide, dexamethasone] can already do? The median PFS is so great for these patients already. How much are we going to add and how much are we going to take away? I still worry about the high-risk, frail patients.
Amrita Krishnan, MD: To your point, I have a case that I have asked a few people about. It’s a patient in their 80s who’s very fit, still working, and has 17p deletion and R-ISS [Revised International Staging System] III disease. I initially started them on daratumumab-Rd until I got the FISH [fluorescence in situ hybridization] test results back. I’m struggling with whether to do the quadruplet now because of the retrospective data in your study looking at lines of therapy and 50% of patients not making it to their second line of therapy.
Krina Patel, MD: Exactly.
Rafael Fonseca, MD: That’s so important, especially in older patients. There’s a new phenomenon that I describe to fellows, that the patient might snap. That’s when you start an older person at 40 mg of dexamethasone, and they absolutely don’t like the treatment. Now you have a hard time getting them to restart treatment. You’ve all seen this in your clinical practice, at family conferences, etc. When we do that, we lose the patient. Those patients go into the attrition count. We have to do it in a gentle way. It’s like fishing. The line has to be tight, but not too tight. That’s what happens. The best treatment of older patients is making sure we can balance toxicities and efficacy in such a way that we get the best results and the patients don’t run away from therapy.
