How I treat MDS: Dr. Shannon McCurdy talks prognostic scoring, ESAs, and more

Thursday, September 10, 2020

Treatment strategies for myelodysplastic syndromes (MDS) vary widely depending upon patients’ prognosis. In this episode, Shannon R. McCurdy, MD, of the University of Pennsylvania, Philadelphia, joined host David H. Henry, MD, to discuss how she treats patients with MDS.

To start, Dr. McCurdy evaluates patients using the revised International Prognostic Survival Scale (IPSS-R), which can predict the aggressiveness of MDS.

  • Low IPSS-R scores (<1.5) are associated with low-risk MDS, which has a median survival of 8.8 years.
  • High IPSS-R scores (>6) are associated with high-risk MDS, which has a median survival of 0.8 years.

Dr. McCurdy also performs molecular testing to assess risk. A poor-risk molecular profile can increase the IPSS-R by 1 point, she said.

Dr. McCurdy went on to explain how she approaches treatment according to risk.

Asymptomatic, low-risk MDS

  • Monitor patients’ complete blood count, typically every 3-6 months, and intervene if there is progression.

Low-risk patients who require treatment

  • Those who have deletion 5q with anemia should receive lenalidomide first.
  • Patients without 5q deletion and low erythropoietin levels (<500 mU/mL) should receive an erythropoietin-stimulating agent (ESA), such as darbepoetin alfa.
  • In patients with loss of response to an ESA, add lenalidomide or granulocyte colony–stimulating factor to ESA treatment.
  • Patients who fail ESA treatment should receive luspatercept.
  • Patients with thrombocytopenia should receive a thrombopoietin mimetic, such as eltrombopag, as a single agent.

Intermediate-, high-, or very-high-risk patients

  • Allogeneic bone marrow transplant is usually done in patients who are aged 75 years or younger, are fit, and want aggressive treatment, Dr. McCurdy said.
  • In patients not eligible for transplant, start a hypomethylating agent (HMA), such as azacitidine, and continue as long as the patients respond.
  • In patients not eligible for transplant who progress on an HMA, consider adding venetoclax.
    • Dr. McCurdy said she doesn’t add venetoclax to an HMA up front because it can reduce patients’ quality of life, but a study presented at ASH 2019 showed high response rates with venetoclax and an HMA in combination (Blood. 2019; 134 [supplement 1]: 4241).

Drugs under investigation

  • Roxadustat, an oral inhibitor of hypoxia-inducible factor, is under investigation in a phase 3 trial of patients with lower-risk MDS (NCT03263091).
  • Dr. McCurdy is involved in a phase 3 trial of magrolimab, with or without azacitidine, in higher-risk patients with MDS (NCT04313881).

Disclosures:

Dr. McCurdy and Dr. Henry have no financial disclosures relevant to this episode.

Show notes by Marianne Riordan, MD, resident at Pennsylvania Hospital, Philadelphia.

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Podcast Participants

David Henry, MD
David Henry, MD, FACP, is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia. He received his bachelor’s degree from Princeton University and his MD from the University of Pennsylvania, then completed his internship, residency, and fellowship at the Hospital of the University of Pennsylvania. After 2 years as an attending in the U.S. Air Force, he was drawn to practicing as a hem-onc because of the close patient contact and interaction, and his belief that, win or lose with each patient, one can always make a difference in their care and lives. Follow Dr. Henry on Twitter: @davidhenrymd. Dr. Henry reported being on the advisory board for Amgen, AMAG Pharmaceuticals, and Pharmacosmos. He reported institutional funding from the National Institutes of Health and FibroGen.