Which Patients Should Be Treated With Luspatercept?

A roundtable discussion moderated by Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center, focused on the latest updates in lower-risk myelodysplastic syndromes (MDS). The panel included Jamie Koprivnikar, MD, of the Hackensack University Medical Center; Solly Chedid, MD, of Singing River Health System; and Thomas LeBlanc, MD, MA, of Duke Cancer Institute.

In the next segment of the roundtable series, the panel discussed which patients should be treated with luspatercept.

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Dr. Garcia-Manero: What is the group of patients where luspatercept should be indicated? Let’s focus on the frontline disease.

Dr. Koprivnikar: Looking strictly at patients included in the COMMANDS trial, these are no brainer patients who should be offered luspatercept upfront. These are patients with very low-, low-, or intermediate-risk MDS. COMMANDS did require that patients be transfusion dependent. However, what we’re seeing as part of real-world data—and what is also supported by some of the wording in the [National Comprehensive Cancer Network] guidelines—is that we may consider giving this treatment even to patients with symptomatic anemia. That’s personally how I practice.

In this group of patients, regardless of [ring sideroblast] status, luspatercept has replaced epoetin alfa or another [erythropoiesis stimulating agent (ESA)] as my frontline treatment of choice. A point we touched upon earlier is patients who have an endogenous erythropoietin (EPO) level of greater than 500 U/L. While these patients were excluded from the COMMANDS study, this was to be fair to the patients randomized to receive epoetin alfa.

Luspatercept is my go-to frontline option for untreated patients with lower-risk MDS with symptomatic anemia. I’m certainly thinking about epoetin alfa or another ESA as second-line therapy potentially before moving to imetelstat for a number of different reasons. For a patient with an EPO level of greater than 500 U/L, I would not be using an ESA, but it is possible that insurers or payers may require the trial and failure of an ESA before they will grant approval for imetelstat.

It’s reasonable to try, although I don’t think we have a lot of data to tell us response rates to ESAs in the post-luspatercept setting. That would be interesting to look at. For patients requiring transfusions who have tried and failed an ESA, imetelstat is certainly a third-line therapy in those groups of patients. There are lots of questions around sequencing. Should we offer an ESA to patients after a luspatercept failure? What are the rates of response going to look like? Should we be going directly to imetelstat? What I outlined is how I would consider approaching that group of patients or treatment sequencing in general. This is certainly up for debate.

Dr. Chedid: At least in my patients, it’s been a no-brainer in terms of using luspatercept in the frontline setting for low-risk MDS. I have gotten some pushback in terms of insurance companies in terms of whether we should use EPO first. From a quality-of-life perspective and efficacy standpoint, that makes huge sense. I’m concerned that by delaying luspatercept to later on, you’re potentially going to have less of an effect for those patients. In the second line setting, I would love to see data on using luspatercept with EPO agents, but it’s nice to have other options available.

Dr. LeBlanc: I agree. The thing I would love to talk to you all about another time would be about the disease-modifying potential of these therapies. As we learn more about imetelstat and the effect on the [variant allele frequency] on the IMerge trial, will that translate into us feeling differently in a year or two or five when there’s more information about whether that has meaningful implications for transformation rates to [acute myeloid leukemia] or survival? We don’t know yet. That could change this up next time we talk and when more data becomes available. Until then, I don’t see a great role for that therapy in the first-line setting. I’m not going to give somebody EPO first to give them that therapy. I’m generally going to give people luspatercept first-line until we learn something we should be doing differently.