Targeted therapeutics in MDS – what’s the current state of play?

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 syndromes (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 azacitidine 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 azacitidine 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.