Zeidan Reviews Past Treatment Options for Patient With Lower-Risk MDS

CASE SUMMARRY

• A 70-year-old man was diagnosed 1 year ago with lower-risk myelodysplastic syndrome with ring sideroblasts (LR-MDS-RS)
  • Multilineage dysplasia
  • Moderate anemia (hemoglobin, 11.2 g/dL) and thrombocytosis (platelets, 500,000/μl)
  • RS in 4% of nucleated erythroid cells
• SF3B1 mutation negative
• Non-deletion 5q
• No family history of cancer or significant genotoxic agent exposure
• In the last 8 months, he received single-unit packed red blood cell transfusions 3 months apart
• Revised International Prognostic Scoring System: low
• Work-up to assess disease status and response to anemia management:
  • Serum erythropoietin (EPO): 250m U/L
  • RS negative
  • Hemoglobin: 8.3 g/dL
  • White blood cell and absolute neutrophil count: within normal limits
  • Platelets: 450,000/μl

Targeted Oncology: How would you treat this patient in your clinic prior to recent data?

AMER ZEIDAN, MBBS: If I saw this patient 3 to 4 years ago, or even last year before the COMMANDS trial [NCT03682536], this is someone I would consider for an erythropoietin-stimulating agent [ESA] for multiple reasons. [However], when the EPO level is above 200 U/L, and certainly when it's above 500 U/L, the ESA is much less likely to work. There isn't a specific cutoff; it's a continuum. The higher the EPO level, the less likely to work. Now the literature is different, but I would say most of the literature, if your EPO level is above 200 U/L, the chance of response [is lower].¹ There are data with ESA where there was no response,² which I don't think is [accurate], because I certainly have seen responders.

But from the COMMANDS trial, which used ESA as a control arm and the response rate was 7% if your EPO level was above 200 U/L.³ It certainly does not work in all the patients. But in the absence before we had luspatercept-aamt [Reblozyl] and imetelstat [Rytelo], what was your other option? You either kept the patient going on transfusions or you gave the patient hypomethylating agents [HMAs]. I am not going to give the patient an HMA as a first-line treatment if they have LR-MDS.

My approach in the past...I would have tried an ESA, and the chance of response [would be] 10% to 15%. If the patient didn’t respond after 3 or 4 months, then I would try something else. This has been my approach [until] the COMMANDS trial. There were some data with epoetin-α; this trial [EPOANE3021] is from Europe.⁴ In Europe, they cannot use drugs until they have randomized phase 3 trials. This trial was only published in 2018, but we've been using ESAs for probably 3 decades for MDS in the United States. It delays the time to transfusions.... For darbepoetin-α, the improvement over placebo was around one-third.² So generally, around 30% to 40% will respond to ESA when they are anemic with LR-MDS. [With the older and] the newer drugs, [those with] the higher EPO level, above 200 U/L, none of those patients responded. But in reality, I would say it's probably 10% to 15%. It's not 0%.

REFERENCES:

1. Park S, Kelaidi C, Meunier M, Casadevall N, Gerds AT, Platzbecker U. The prognostic value of serum erythropoietin in patients with lower-risk myelodysplastic syndromes: a review of the literature and expert opinion. Ann Hematol. 2020;99(1):7-19. doi:10.1007/s00277-019-03799-4

2. Platzbecker U, Symeonidis A, Oliva EN, et al. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia. 2017;31(9):1944-1950. doi:10.1038/leu.2017.192

3. Platzbecker U, Della Porta MG, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10399):373-385. doi:10.1016/S0140-6736(23)00874-7

4. Fenaux P, Santini V, Spiriti MAA, et al. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS. Leukemia. 2018;32(12):2648-2658. doi:10.1038/s41375-018-0118-9