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Therapies and Treatment Regimens for MDS


A broad review of agents and regimens used to manage patients with myelodysplastic syndrome.


Bart Scott, MD, MS: The main types of chemotherapy we use for patients fit into a broad category called hypomethylating agents. There are other treatments that patients may receive, like growth factors, GCSF, and erythropoietin. There are a minority of patients, typically younger, who have pancytopenia who would receive immunosuppressive treatment, for example. Then there are new medications that are approved like luspatercept, which stimulates red blood cell production that would fit into the type of a growth colony stimulating factor. There is a drug called eltrombopag that is also sometimes used to treat patients.

In regard to actual chemotherapy, that’s hypomethylating agents. There are some patients with MDS [myelodysplastic syndrome] who may be young, who have very aggressive disease, almost what we would call acute myeloid leukemia [AML], that would fit into a category of MDS-EB1 or MDS-EB2 that we might get more treatments that are like AML. We call that AML-induction chemotherapy.

In regard to chemotherapy, there are 2 main choices: hypomethylating therapy and induction chemotherapy. The hypomethylating therapy can be given in combination with another drug called venetoclax. In regard to who should receive chemotherapy and who should not, that’s a complicated discussion. The physician would consider the overall risk of the patient by their disease. We would use the revised IPSS [International Prognostic Scoring System] risk. It would be patients who are in higher-risk categories who would be chosen to receive either hypomethylating therapy or induction chemotherapy.

There is another component we consider, and that would be the underlying health of the patient. What type of comorbidity do they have? Would they be able to tolerate induction chemotherapy or hypomethylating treatment? Hypomethylating therapy, in general, has a low toxicity profile, is relatively safe, and is probably underutilized in the treatment of MDS patients. Many patients who are “too old” or have “too many comorbidities” are probably incorrectly placed into those categories. There are many MDS patients who should probably be treated with hypomethylating therapy, for example, but are not. We’re probably not as aggressive in treating MDS patients as we should be.

Just to extend what we’re talking about with hypomethylating agents, there are 2 approved hypomethylating agents: azacytidine and decitabine. More are expected to be approved in the near future, and we are working on the oral administration of hypomethylating agents, which should improve access and compliance to care.

Amer Zeidan, MBBS, MHS: Aside from hypomethylating agents for high-risk MDS, there are no treatments that are approved aside from bone marrow transplantation. You have to be in a complete remission generally for bone marrow transplantation to work the best in patients with myelodysplastic syndromes. The lower the burden of the disease, the better. You can achieve that sometimes with hypomethylating agents, but the overall response rate is around 50%. Only 20% achieve complete responses, so many patients will not achieve a complete response, and that’s hitting a hypomethylating agent failure, which could be primary, meaning you do not respond from the get-go, secondary failure or resistance in which you responded initially, but you lost your response. Those are very challenging. The median survival for such patients is limited in the range of 4 to 6 months, and we don’t have any approved treatments in this setting. For some of the younger patients or the patients who are able to tolerate other intensive treatments, we can give them intensive chemotherapy. However, because of the age of the patients and the intensities of these therapies, many patients might not be able to tolerate anything. It’s a very difficult situation, and a lot of clinical trials are ongoing, and they’re setting to look at new agents.

For lower-risk MDS, erythropoietin-stimulating agents [ESA] are often used for anemia. If you look at older patients with lower-risk MDS, around 40% of patients would respond to these agents with the fusion independence. You can select patients who have lower total erythropoietin level or have frequent transfusions; those patients tend to respond better when you give an ESA, but the response is generally temporary. It lasts somewhere between 12 and 18 months; the patients will lose response eventually and need something else.

Lenalidomide is active when you have deletion 5q lower-risk MDS in which transfusion independence can occur in almost two-thirds of the patients. However, on deletion 5q MDS, the response rate to lenalidomide, which is an oral agent, so it’s easier to administer, can be only around 25%, and the response duration is around 30 to 40 weeks. It’s limited. Another drug that was approved just recently, a few weeks ago in early April, luspatercept, is transforming growth factor beta. What this agent does is it traps ligands for the transforming growth factor pathway and has been shown to lead to transfusion independence in around one-third of patients with lower-risk MDS if they have ringed sideroblasts; that’s a subtype of lower-risk MDS. This has become a treatment option that’s available, and it’s being used currently in the community.

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