During the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, the MDS Hub was pleased to speak to Theo de Witte, Radboud University Medical Center, Nijmegen, NL. We asked, Is there confusion between the World Health Organisation (WHO) and Molecular International Prognostic Scoring System (IPSS-M) classifications of myelodysplastic syndromes (MDS)?

De Witte begins by discussing the basis of the current IPSS-M criteria on cytogenetics characteristics, blast percentage, and severity of cytopenia, despite half of patients diagnosed with MDS having normal karyotypes. Moving on, De Witte compares the IPSS-M with the recently updated WHO classification and its focus on diagnosis and morphological features. De Witte emphasizes the importance of identifying specific genetic mutations to determine prognosis more accurately, omitted from the WHO classification.

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There is a need for international guidance in MDS​. The MDS Europe guidelines are accessed all around the world, with high readership in the US, India, and China​. The MDS International Guidelines will meet this global need, providing community-based hematologists, internists, healthcare professionals, and doctors in training with accessible international guidance.​

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During the 2021 ASCO Annual Meeting, the MDS Hub spoke with Jacqueline S. Garcia, Dana-Farber Cancer Institute, Boston, US, and Amer M. Zeidan, Yale School of Medicine, New Haven, US. We asked, How can the hematologic toxicities with Ven+Aza be managed more effectively.

Garcia discusses data from a dose-escalation phase Ib study (NCT02942290), evaluating Ven+Aza for the treatment of treatment-naïve patients with high-risk MDS. Garcia reports the promising efficacy and safety results seen in the trial.

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During the EHA2021 Virtual Congress, the MDS Hub spoke with Uwe Platzbecker, University of Leipzig Medical Center, Leipzig, DE. We asked, What hematologic toxicities occur after venetoclax + azacitidine in MDS and how can they be managed?

In this podcast, Platzbecker discusses the potential hematologic toxicities associated with the combination of venetoclax and azacitidine, and how to manage these toxicities in patients with high-risk MDS. He highlights the key points of a study presented during EHA2021, including dose modification considerations, overall response rates, infectious complications, and other side effects. Finally, Platzbecker believes this toxicity analysis provides clinically valuable information to doctors and hematologists who are already treating patients with this combination.

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During the EHA2021 Virtual Congress, the MDS Hub spoke with Vinod Pullarkat, City of Hope Comprehensive Cancer Center, Duarte, US. We asked, What hematologic toxicities occur after venetoclax + azacitidine in MDS and how can they be managed?

Pullarkat discusses the hematoloigc toxicities associated with venetoclax and azacitidine, which are largely related to cytopenias. He explains that the key to managing these toxicities is close monitoring of patients and providing transfusion support as needed. Finally, he mentions that a high percentage of patients will require dose modifications.

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During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the MDS Hub spoke to Pierre Fenaux, Université de Paris, Paris, FR, about the new advances for treating patients with low-risk MDS.

Low-risk MDS is characterized predominantly by anemia or thrombocytopenia, fatigue, cardiovascular complications, and the need for regular transfusions. In this podcast, Fenaux discusses the new treatment options to prevent anemia. He starts with erythropoietin and its derivatives, which yield responses in about 60% of patients. He also mentions lenalidomide for patients with 5q deletion, and luspatercept, another promising drug that will soon be available in Europe. Fenaux continues with roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, which showed promising results in a phase II study. He also discusses the use of hypomethylating agents, with response rates of up to 25% for patients who have mainly anemia.

For the minority of patients with predominant thrombocytopenia, the recent use of thrombopoietin receptor agonists yielded response in around 50% of cases, with limited side effects. Finally, for young, low-risk patients that do not respond to treatment and have severe thrombocytopenia, Fenaux highlights allogeneic stem cell transplantation as a treatment option.

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During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the MDS Hub spoke to Valeria Santini, University of Florence, Florence, IT, about tailoring treatment to improve outcome in MDS.

Santini starts by saying that, despite significant improvements in the tools available to physicians to select the optimal MDS therapy, the results obtained are still not always satisfactory. She highlights that the first step for a tailored treatment is stratifying patients prognostically, depending on their risk level and somatic mutation evaluation.

Santini then discusses tailoring anemia treatment according to the MDS subtype and mutations present. She also points out that the number of somatic mutations correlates with overall survival, and that being able to identify the number of somatic mutations allows healthcare professionals to speed up the decision and choice of treatment. Azacitidine or decitabine represents the standard of care, but a proportion of patients do not respond. However, these patients can respond quite well to azacitidine combinations. Therefore, Santini highlights the studies looking at azacitidine combinations to increase responsiveness.

Santini concludes with a remark on how bright the future is looking for treating patients with MDS given the abundance of new therapeutic options and the development of a novel prognostic system.

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During the 2020 Annual Meeting of the Society of Hematologic Oncology (SOHO), the MDS Hub podcast channel spoke to Dr David Sallman, Moffitt Cancer Center, Tampa, US, and Professor Amer Zeidan, Yale School of Medicine, New Haven, US, about current therapeutic options for treating frontline and relapsed/refractory myelodysplastic syndrome (MDS).

Sallman starts by asking how venetoclax or other BCL-2 inhibitors can be used to treat patients with high-risk MDS. Zeidan addresses this question with reference to two phase Ib studies that are currently underway, in which azacytidine was combined with venetoclax. He highlights the age and increased frailty found in MDS patients compared with average patients with acute myeloid leukemia (AML), and the stringent requirement of prophylaxis against infection. The second phase Ib study was carried out in the relapsed/refractory setting in a small group of patients, and the survival outcomes are described. Zeidan states that the initiation of a large phase III trial in the frontline setting should provide more information.

Zeidan then asks Sallman about what other agents are showing promise for the treatment of high-risk MDS, focusing on magrolimab and APR-246. Sallman describes how these agents can act synergistically with azacytidine and their relationship with 'pro-eat me' signals. He also points out the positives regarding the safety profile for these treatments and response rates, and lists a few upcoming trials with these agents.

Following this discussion, Amer Zeidan brings the conversation around to pevonedistat and MBG453. The results from the phase II trial for the former were presented at the European Hematology Association (EHA) and the American Society of Clinical Oncology (ASCO) conferences this year, but Zeidan is still waiting for the phase III data to draw more concrete conclusions on its value. The immune checkpoint inhibitor MBG453 is also undergoing clinical testing, and Zeidan gives some details of several trials with this agent.

Zeiden next asks Sallman what new agents are the most exciting in his opinion. Sallman describes how bright the future is looking for treating patients with MDS given the abundance of new therapeutic options, and how these might be best used in triplet or sequential therapy.

Sallman then asks for Zeidan's closing thoughts.

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