Goals and Duration of Treatment for Elderly Patients with Transplant-Ineligible NDMM
The panel explains their goals of treatment for older patients with transplant-ineligible multiple myeloma, and how they determine treatment duration.
Rafael Fonseca, MD: Dr Costello, what are your goals of treatment once you start one of those regimens?
Caitlin Costello, MD: In an ideal world, the goal is no different from that of a transplant-eligible patient. We’re still trying to achieve deep and durable responses. It’s a bit of the finesse you’re talking about of trying to figure out how we can achieve those results without adding excess toxicity. In the end, do no harm. We’re trying to do good. We’re trying to save lives. But we aren’t doing any benefit to our patients by making them feel sick. I always say that I don’t want the drugs to be worse than the disease.
Realistically, not every 80-year-old is the same. You can have an 81-year-old, full-time working person who very well could tolerate a quadruplet [regimen]. Maybe those people are worth the chance where you go big from the get-go to try and make a real dent in the disease if you think they can tolerate it. With some patients, you can get a good sniff test, where they walk in and you say, “No, this isn’t going to be an 80-year-old who’s going to tolerate a quadruplet,” for example. Even with high-risk disease, sometimes you put your best foot forward with a triplet, which has great outcomes, and see if you can make a good impact on their disease. Ultimately, it’s a very careful balance between the successes of the treatment and the toxicity.
Rafael Fonseca, MD: We’re all scratching our heads because you see the results of the MAIA trial, for instance, and you start looking at overall survival [OS] vs actuarial projected survival. If someone was diagnosed in the second half of their 70s or early 80s, it isn’t far-fetched to think that they’re getting pretty close to their life expectancy at that point. We did a simulation using real-world data and projected a median overall survival of about 9.1 years with MAIA. If you’re in your 80s and you have standard-risk factors and you can tolerate the monoclonal, which we’re saying is well tolerated, you’re getting pretty close.
For me, the biggest question right now is patients who are 70 to 75 years old if they don’t look like patients who are spinning 5 times a week, hiking, etc. Do you take them to transplant, or do you use regimens? Dr Krishnan, you’re a transplanter. What are your thoughts on the transplant suitability for patients who are 70 to 75 years old?
Amrita Krishnan, MD: You’re right, that’s a challenging group. There are data from the Mayo [Clinic]. There are some CIBMTR [Center for International Blood and Marrow Transplant Research] data retrospectively saying the tolerability of transplant is equal in the older and younger patients. Obviously, those are very selected patients. We do about 500 transplants a year in that 70- to 75-year-old age group from CIBMTR data in the United States. The easy part of that discussion is that it isn’t a question of early vs delayed transplant. I always say if we’re going to do it, this is the window in which we’re going to do it. I do quote determination in terms of PFS [progression-free survival], and I don’t think it’s unreasonable in that group of patients to do it. There are certain patients who elect to do it. I’m a little more liberal in terms of looking at the MAIA data and saying a nontransplant approach isn’t wrong as well. In our practice, it’s probably about 50/50.
Rafael Fonseca, MD: Going back to your point, as you look at patients who are candidates for this treatment, let’s say you move them through a nontransplant approach. What should be the duration of therapy? I don’t think anyone knows. We know what’s published, and we’ve alluded to that. What are your thoughts on how long we should treat this patient? Because we know longer treatment is better in general, but there’s more toxicity to it as well.
Amrita Krishnan, MD: With those groups of patients, I continue therapy with the idea of probably dropping the things that are causing the most adverse effects, trying to reduce the steroids as much as I can, having low thresholds in terms of the IMiDs [immunomodulatory imide drugs] at a certain point, and then basically keeping the antibody going. Having said that, COVID-19 changed a lot of things for us. In the last couple of years, our practice has shifted a lot in terms of how we look at antibody therapy and risk. We’re shifting back, or maybe at least somewhere in the middle, in terms of risk-benefit. But we also can’t underscore infection risk, especially in an older patient.
Rafael Fonseca, MD: We have good data on discontinuation of steroids. No one likes steroids, particularly family members. Let me go back to one point that you made. Dr Krishnan, this is a transplant-ineligible patient, but your thought was that if you’re going to do a transplant, do it up front. I can’t see a lot of rationale for saying, “I’m going to save transplant for later.” Maybe it’s good to save stem cells. We’re going to talk about some of the relapsed/refractory disease. But if you’re going to do it, do it now.
Amrita Krishnan, MD: If you’re 70. Otherwise, I’m going to say, “Go to The University of Texas MD Anderson Cancer Center. They’ll probably show their data of the 80-year-old transplant population.” My enthusiasm diminishes once you get over 75 years old because of fewer data and probably less OS benefit at that point.
Rafael Fonseca, MD: You start dropping. It should be almost MEL 200 [melphalan 200 mg/m2] eligible. Because once you start going to MEL 140 [melphalan 140 mg/m2]—there are all sorts of conversations that can be started about PK [pharmacokinetics] and PD [pharmacodynamics] for melphalan—you might not be dealing with the same type of treatment as well. Dr Patel, let me go back to the original question. What are your thoughts on duration of therapy in older patients?
Krina Patel, MD: If they’re tolerating it well and not having major issues, we keep going, because we know that being on it is why they’re doing so well on trials. I try to emulate that. But a lot of my patients over time start having neutropenia and more infections. We try to give them the best supportive care, such as IVIG [intravenous immunoglobulin]. But then I start dose reducing pretty quickly. I try to get them to their best response. If I can do that in a year, great. Then again, it goes by toxicity. I have some patients for whom we’ve stopped all therapy. Sometimes an 80-year-old can’t come in every month. They don’t have family that can bring them in. If they’re doing it, they have a really great response. If they’re tolerating it well and not having toxicity, we keep going.
Rafael Fonseca, MD: It’s always humbling to practice in myeloma treatment. People stop therapy and are doing great years later. You think, “How many more could do that?” To finish this part, Dr Costello, what are your thoughts on duration of therapy?
Caitlin Costello, MD: Exactly what everyone said. The only thing I’d add is that sometimes this is where the negotiations start. We talk about dexamethasone going first, and then the conversation moves to “Can we reduce the Revlimid? Do I really need the Revlimid? Can I just stay on a once-a-month shot instead?” I have that conversation. I say, “I’d love to keep you on therapy, but let’s try to find a happy middle ground for you.” Sometimes patients just want to stay on the daratumumab shot.
Amrita Krishnan, MD: Something we underrepresent that also frightens me is anticoagulation in older people.
Krina Patel, MD: Exactly.
Rafael Fonseca, MD: Great point.
Amrita Krishnan, MD: Putting an 80-something-year-old on it is probably much more frightening to me than giving daratumumab.
Caitlin Costello, MD: With a walker, who’s going to fall.
Rafael Fonseca, MD: It isn’t the topic for today, but then you have questions, is aspirin an option? Should we use DOACs [direct oral anticoagulants]? If you have DOACs, then you have falls. Then we’re talking about a whole set of other things.
