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FAQs: MDS Emerging Data
Myeloid Malignancies Clinical Advances Journal Club on Emerging Data for MDS: Answers to Frequently Asked Questions

Released: July 22, 2024

Expiration: July 21, 2025

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Key Takeaways
  •  IPSS-M is a useful tool for accurate risk stratification of patients with MDS; IPSS-M may help inform treatment decisions in patients with high-risk MDS who may be considering a transplant
  • In patients with lower-risk MDS and MDS-related anemia, ESAs, luspatercept, and imetelstat are all effective treatment options
  • In a real-world setting, carefully increasing to a higher dose of luspatercept (from 1.0 mg/kg to 1.75 mg/kg) is often required for achieving activity if there is no response after 6 wks with the starting dose

Assessing and integrating new clinical data for individualized care of patients with myeloid malignancies has increasingly become more important with the frequent release of clinical trial data updates, real-world reports, and emerging new options for patients with myelodysplastic syndromes (MDS). In this commentary, we share answers to frequently-asked questions (FAQs) posed by a live audience of healthcare professionals on key emerging new data presented for MDS at the 2024 ASCO annual meeting and the 2024 EHA congress, including our takeaways for practitioners looking to stay up-to-date with the data presented at these summer conferences.

What is the current use of molecular international prognostic scoring systems (IPSS-M) at your institution?

Courtney DiNardo, MD, MSCE:
At our center we use IPSS-M, which integrates the mutational information captured by next generation sequencing (NGS), in addition to calculating the standard (IPSS) and revised (IPSS-R) scores. We have found that in some patients the IPSS-M score can make a big difference in regard to risk stratification. For instance, in a patient that may be low- or intermediate-risk by IPSS and IPSS-R scoring, respectively, having specific mutations detected by NGS entered into the IPSS-M calculator may result in the patient being reclassified under a higher-risk category. I think it is increasingly important to know the molecular mutation status of patients with MDS. We do not have as many targeted treatments for MDS as we do for AML, but knowing SF3B1, TP53, and IDH1 mutation status in conjunction with morphologic findings like excess blasts or ring sideroblast status is very relevant for this disease. We have been considering IPSS-M particularly for younger patients, in those who may be receiving a transplant consult, and for those who may be starting hypomethylating agent (HMA) earlier in the course of their disease. IPSS-M status is displayed in a very easy to intuit weblink, and may be something that patients may want to reference, particularly in patients who are interested in knowing all the relevant statistics and expectations relevant to their disease.

At the live webinar, healthcare professional answers to a polling question on NGS testing showed that almost half of patients with newly-diagnosed MDS are not being evaluated by NGS testing. I was of the opinion that NGS testing was more of a standard practice across the board, but I suspect that access (eg, lack of insurance coverage) and the fact that we do not yet have targeted therapies for most of the abnormalities identified are impacting adoption of this practice.

Brady L. Stein, MD, MHS:
My practice is a little bit different than Dr. DiNardo’s because I see mostly patients with classical hematologic disorders and myeloproliferative neoplasms (MPNs). I can address the question as it pertains to MPNs because our situation is similar in that our prognostic scoring systems have also evolved. We now have a similar prognostic scoring system that includes results from NGS and I agree that this information is very important for prognostic assessment of our patients. We have so much heterogeneity in these diseases and having molecular data can help us to reclassify the disease into different risk groupings. We also use this information when discussing transplant as an option for our patients with myelofibrosis.

The bottom line is that if we are looking at just patient demographics and blood count abnormalities that is just not going to tell the whole story for the patient with MPNs. 

Do you add luspatercept to an erythroid stimulating agent (ESA) or use it as a single agent in patients with MDS and MDS-related anemia?

Courtney DiNardo, MD, MSCE:
In patients with lower-risk MDS, ESAs, luspatercept, and imetelstat are all effective treatment options particularly in those with anemia. I primarily use either luspatercept or ESA as a single agent. I have not started using them together in combination but this is an important area of research.

Luspatercept was associated with improved rates of red blood cell transfusion independence and increased hemoglobin levels compared to erythropoietin in ESA-naive patients, which was confirmed in the follow-up from the multicenter phase III COMMANDS trial. Data presented at EHA 2024 by Dr. Patel and colleagues showed that in a real-world setting, higher doses of luspatercept are often required for efficacy. You can start luspatercept at 1.0 mg/kg subcutaneously every 3 weeks and if they do not respond at that dose after 6 weeks, you can increase from the 1.0 mg/kg dose to 1.33 mg/kg and then to a maximum dose of 1.75 mg/kg according to the package insert. Imetelstat is an option for patients with lower-risk MDS with transfusion-dependent anemia that have not responded to ESAs and that is associated with red blood cell transfusion independence―in approximately 40% of patients. And then HMA agents like oral azacitidine may be an option in the setting of failure of the above options for patients with lower-risk MDS. 

There is exciting early clinical data exploring the combination of luspatercept and ESA for patients with low-risk MDS and anemia from the Moffitt Cancer Center. I think that this could be a very effective strategy moving forward. Another combination of interest is being evaluated in the multicenter, randomized, phase III SELECT-MDS-1 study of tamibarotene plus azacitidine vs placebo and azacitidine for newly diagnosed RARα-positive higher-risk MDS. Initial clinical data in this patient population showed that tamibarotene plus azacitidine yielded high complete response rates in newly diagnosed RARα-positive, unfit, higher-risk MDS including ≤30% blast count AML, with most patients achieving or maintaining transfusion independence.

Your Thoughts?
What are your thoughts or questions on the emerging data for patients with low-, intermediate-, and high-risk MDS? Answer the polling question and join the conversation by leaving a comment. Also, feel free to visit the program page to view an on-demand webcast from the live event, download the associated slides, read other clinical commentaries, or listen to podcasts on emerging data for MDS, AML, and MPNs.

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