What Is the Current MDS Treatment Landscape?

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 first roundtable segment, the panel discussed the current state of MDS treatment.

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Dr. Garcia-Manero: Can you please give us an overview of what is happening in low-risk MDS?

Dr. Koprivnikar: All of a sudden, we have a lot of treatment options for patients with lower-risk MDS. This is a field that was largely ignored for transfusion-dependent patients. We did not have a lot of great options. The de facto standard of care three or four years ago was therapy with erythropoiesis-stimulating agents (ESA) and transfusion support. If that failed, we would consider disease-modifying therapies like hypomethylating agents (HMAs). The notable exception was patients who had del(5q) MDS who have shown to benefit by more targeted therapy with lenalidomide in terms of anemia.

More recently, there have been some major developments. A few years ago, luspatercept was approved in lower-risk, transfusion-dependent patients with ring sideroblasts (RS). This was in the second-line setting for patients who had tried and failed an ESA or who were deemed ineligible for an ESA based on an elevated erythropoietin level. More recently, seeing how well luspatercept performed in this particular group of individuals in the MEDALIST trial, there was a much broader trial of luspatercept undertaken in the frontline setting for all comers with lower-risk MDS.

Again, patients could have very low-, lower intermediate-, non-deletion, 5q-risk MDS. They had to be ESA-naive and have an EPO level of less than 500. As part of the COMMANDS trial, patients with lower-risk MDS were randomized to receive either luspatercept or weekly epoetin alfa (EA). Patients saw an improved response rate with luspatercept compared to ESAs. The COMMANDS trial established a new potential frontline standard of care for patients with lower-risk MDS who may require transfusions.

More recently, we’ve had the approval of imetelstat, a telomerase inhibitor. This group of patients is quite distinct from those included in the COMMANDS study. Whereas COMMANDS enrolled patients who were ESA-naive, the IMerge trial that led to the approval of imetelstat enrolled patients who were either ineligible for or refractory to ESAs. We saw about a 40% response rate in terms of a period of transfusion independence.

Over these past several years, we’ve had some practice-changing developments in the field of lower-risk transfusion MDS and in patients with MDS who have symptomatic anemia. It’s an exciting time to be treating these patients, and I’m glad that our patients have more options.

Dr. Garcia-Manero: Wonderful. We’ve gone from only ESAs to now luspatercept in frontline patients. This drug is extremely active in RS-positive disease, but data published in The Lancet Hematology indicates that this drug is also highly effective in the RS-negative group of patients. We have that in frontline disease and imetelstat in second-line disease.

In the IMerge study, a majority of patients were also predominantly RS-positive, which is interesting. That’s an important major development. Of course, we still have the ESAs for patients who will benefit from these ESAs and lenalidomide for those with del(5q) minus disease.

There was a recent study from Europe published in The Lancet Hematology with the early use of low-dose lenalidomide 5 mg in transmission-dependent patients with del(5q) disease. That’s quite important. Of course, we have the HMAs that have been part of what we do for many years. Younger patients may be candidates for transplantation. We have patients with hypoplastic MDS that we tend to treat like aplastic anemia. All of a sudden, as Jamie was saying, the armamentarium is complete now. We need better drugs for low platelets and things like that.

I would like to ask our experts for their perspective. The first one is for Solly. What is your perspective as a more community physician dealing with these new drug developments for patients with MDS? How do you think they have been or are being incorporated in your practice?

Dr. Chedid: Aside from initially making the diagnosis and making sure that other confounding factors aren’t being addressed, knowing when to refer patients to centers of excellence is important. I think that’s where the Molecular International Prognostic Scoring System (IPSS-M) excels. In the Revised IPSS, were missing some patients that were high risk. I think those were being captured with better fidelity with the IPSS-M. For patients who initially looked like they were going to do relatively well and weren’t doing well, we should refer them much earlier to transplant or treat them as high-risk MDS rather than low-risk.

Most of our patients are presenting with anemia, so they’re presenting feeling bad. Especially in my practice, many of these patients already have chronic obstructive pulmonary disease or congestive heart failure. Even with a hemoglobin below 10, they’re very symptomatic. Raising their hemoglobin by 1, 1.5, or 2 is a big deal when we can keep that elevated, especially with agents like luspatercept that can keep their hemoglobin raised for a protracted period of time. From my perspective, it’s all about quality of life and keeping patients out of trouble for a longer period of time.

Sequencing is certainly going to be a challenge, and I would love to get your input on that as well in terms of which insurance companies would like us to use the least expensive product upfront. At the same time, the patients are having to come in every single week, 52 visits a year, compared to potentially only 17 visits a year for luspatercept. From a quality-of-life perspective, the opposite side is being able to raise the hemoglobin a little faster and longer with luspatercept and having far fewer visits. It’s about helping patients have the best quality of life they can.