ASH 2022 | Promising agents under investigation for low and high-risk MDS

There is plenty of trials with MDS and obviously I cannot point out a particular trial. I can say, and I can split it to several groups of trials. In the lower risk patients, we know that we treat these patients with blood transfusions. We treat these patients with erythropoietin or ESA as first line. And in many countries, luspatercept has become the second line. But considering that about 50% of the patients do not respond, and even those who respond lose their response on the average after two years, there is a room for many other agents. And fortunately there are now several interesting clinical trials testing in various aspects of these patients who do not respond anymore to ESA or to luspatercept.

So, I would like to mention a clinical trial with the agent roxadustat, which is a HIF inhibitor. I would like to mention the imetelstat, which is a telomerase inhibitor. Several studies are trying to use oral hypomethylating agent as well as hypomethylating, which are usually used in higher risk patients, but they are now used also in trials. I’m not saying standard therapy in low risk patients, there is a new agent, which is based on RNA splicing and also some more targeted agents such as anti or targeted agents for the IDH2 and for other mutations. I believe that in the next few years we will see number one, combinations and number two, more targeted agents towards specific mutations such as TP53, IDH1 and 2, and other mutations. So, I’m not sure that it’s a good idea to be sick, but I think that the future looks much better. This is for the low-risk patients.

Now, as for the higher-risk patients, as we all know, hypomethylating agents have become the standard of care. But again, the good news that we have an effective agent, the bad news that the response rate is still around the 50% and the response duration is around two years at best. So there is still much to be done, to do better. And there is a long list of trials, testing basically additional agents to hypomethylating agents. Many trials still use the venetoclax as another agent in addition, others are using other agents. We just heard by the group from MD Anderson, Phase I trial on new agents, oral agent, which combines azacitidine and cedazuridine with additional agents. So, I think we will have a list of agents which are tested in highrisk patients, and hopefully in the next few years we will come to a conclusion what is the best combination. And I hope that we will be able to break this line of 50% in two years and we will do better. So, I hope that future really looks better.