Around the Practice: Optimizing First-Line Therapy in Transplant-Ineligible Multiple Myeloma - Episode 2
Panelists elucidate how to determine transplant ineligibility and the goals of therapy while managing a patient with multiple myeloma.
C. Ola Landgren, MD, PhD:I was teasing you a little, Cristina, when I said, “Are there any transplant-ineligible patients?” We’ve gotten better specialists in myeloma. You could transplant medically a fit 75-year-old or close to 80-year-old, but then you have all these other options. You could make the same case for younger ages, although you could say that’s standard care…. There’s no clear-cut question all the time. In my practice, if an older patient comes says, “I want to collect and store stem cells,” I usually say, “For what?” You’re going to store them for 5 years. That might not be the right thing? What do you think about that, Cristina?
Cristina Gasparetto, MD: I agree. Sometimes when I have an older patient, I have that conversation. When they want to store their stem cells, I say, “You’re not getting any younger. You’re getting older.” If you’re storing the stem cells at age 74, I’m not going to do the transplant in 2 or 3 years. It’s a decision of the moment. But you’re correct. Sometimes, we smile when we do transplant in older patients, but we need to select them because even if they look good and fit, during the transplant they melt away. It’s different—you’re 70-plus years old. Even in good condition, you give high-dose chemotherapy and they age dramatically over a few weeks. I saw that multiple times: very fit patients completely lose everything during the transplant because they don’t have any reserve. With the new combinations going away from transplant in this particular population, it makes absolute sense for quality of life.
C. Ola Landgren, MD, PhD:What makes a patient ineligible for a transplant? Peter, in your practice would you say there’s a general consensus on that?
Peter Voorhees, MD: As you’ve all discussed, I don’t think age is what we should be using to determine transplant eligibility. It’s just a matter of fitness, and we have to do a good job of determining that level of fitness. Having a conversation with the patient in the clinic room and giving them an ECOG performance status of 1 is not sufficient. These geriatric assessment scales that are available—and there are a number of them available—are more rigorous in determining the frailty of the patient. The IMWG [International Myeloma Working Group] has its own frailty score, which is used for and associated with worse outcomes and higher rates of severe toxicity with therapy for those who are frail. We need to employ those in the clinic more often. Then we can do a better job of determining those patients who can go through a transplant safely and those who would be harmed from a quality-of-life perspective.
C. Ola Landgren, MD, PhD:Craig, in your clinic are there any measures—that we’re bringing up here—that you’d agree aren’t good markers? Are there any organ system measures that you would look for in your clinic? What do you think about that? Cardiovascular or renal, things like that.
Craig Hofmeister, MD, MPH: In our group we’ve struggled with this because the pharmacokinetics and melphalan are difficult to predict, and they certainly depend on patients’ kidney function and hemoglobin. Age isn’t 1 of the things it depends on. When you eliminate somebody by age alone, that may not be the best choice. When we’re thinking about transplant, we’re looking at performance status and the dosing of melphalan related to kidney function. Less than 40% ejection fraction is a spot where it’s hard to be excited to expose somebody to 200 mg/m2 of melphalan. With compensated CHF [congested heart failure] and left ventricle ejection fraction at greater than 40%, you might be able to ease away 140 mg of melphalan. The big question is for those folks with some evidence of nonalcoholic steatohepatitis. Are they heading in that scleroses category? That’s a challenge for me in induction and at the time of transplant, because their transaminases and bilirubin aren’t all that sensitive. Some elastography seems to be a better way to go.
C. Ola Landgren, MD, PhD:Thank you. I have several things written down that I want to discuss. I had initially thought I should ask you about the goal of frontline therapy in this patient population.… But based on the conversation we’re having, we’re all saying that we want to drive down the disease with a good response. Maybe it’s also a matter of causing less harm with fewer adverse effects because of patients being less strong. If they’re a little frailer and they’re thin, they’re not that different from younger patients. But keep in mind, if we have to choose between efficacy and toxicity or a little bit less efficacy and toxicity, we’ll probably choose the second of those 2, at least in more frail patients. If there are no limitations, we’ll go full speed as we would do with a young transplant-eligible patient.
Transcript edited for clarity.