MDS Treatment Advances: Targeted Therapies and Anemia Management

Treatment for myelodysplastic syndromes has gradually advanced in anemia management and targeted therapies, according to Dr. Jorge Cortes, deputy chair of the Department of Leukemia at the University of Texas MD Anderson Cancer Center and director of the Georgia Cancer Center at Augusta University.

Hypomethylating agents remain standard, while newer drugs like Rytelo (imetelstat) and therapies for IDH1/IDH2 mutations expand options. Clinicians balance treatment effectiveness with quality of life, considering age, comorbidities and disease severity. Ongoing research may offer new avenues for longer survival and potential cures.

CURE: How has the treatment landscape for MDS evolved in recent years, particularly regarding targeted agents and novel therapies?

Cortes: Unfortunately, with MDS, we have not made as much progress as in other diseases. Our standard treatment has been with the use of these drugs that we call a class of hypomethylating agents, like cytidine and the cytopen. They work, and they give responses to many patients and prolong survival. But we are trying to look at better options that can improve survival.

We have made progress in some areas, for example, in the management of anemia, which is a very common problem and something that really impacts the quality of life of patients. We have been able to develop new drugs that help patients who have that issue. A few years ago, one drug came along, and now we have a more recently approved drug, Rytelo. Both of them are very good. They each have their pros and cons, but generally speaking, they are very good additions to our armamentarium for managing anemia.

In that regard, we have made very good progress for patients who have certain abnormalities, like mutations in some genes. One example is a gene called IDH, which can be IDH1 or IDH2. There are treatments that target those mutations, which also happens in AML, and patients can respond well to drugs that are now available for that. So we've made some progress. I think for many patients, we are still looking at the right combinations that can help us make the next big leap in improving survival and eradicating the disease, short of a stem cell transplant.

Are there any other unmet needs within MDS care that you think are important to focus on, and is any ongoing research aiming to address these challenges?

There is a lot of research going on, and I am optimistic that we are going to start finding better treatments. One of the challenges is that even in laboratories, MDS is a disease that’s difficult to study — more difficult than some other cancers. There are not great models to test drugs and understand disease behavior, but there are many good attempts at developing new drugs. Some have given us promise but then end up not panning out the way we wanted.

However, there is a lot of research now with new targets and new developments. I am very hopeful that in the next few years we are going to start seeing a big leap forward in the probability of long-term survival and eventually cure.

Given the disease's chronic nature, how do clinicians aim to balance treatment efficacy with quality-of-life considerations?

One of the things with MDS is that it’s a disease with a wide spectrum of manifestations and possible outcomes. In the early stages, it is very indolent, sometimes only causing mild anemia or issues that may not even need immediate treatment. On the other side, there are forms that are much more aggressive and behave a lot more like acute leukemia.

So that balance comes in part from considering where a patient falls in that spectrum. Another important factor is that many of our patients are older, with other comorbidities and medications, which may limit the intensity of treatment or options — like stem cell transplant — not being possible. All of these factors have to be balanced so you can offer the best option to a patient, with a risk-benefit ratio that most favors them.

But, yeah, it is a very complex and heterogeneous disease, not to mention the genetic abnormalities and other factors that add further complexity. That has been part of the reason why it’s been so hard to make big leaps forward in MDS.

Transcript has been edited for clarity and conciseness.

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