Jing Ai, MD
Hypomethylating agents are a standard treatment for patients with myelodysplastic syndrome (MDS), but lenalidomide (Revlimid) has been shown to be a viable option in those with and without deletion 5q, said Jing Ai, MD.
But while lenalidomide is effective in clinical practice, the use of hypomethylating agents is “not going to go away in the field,” Ai said.
Azacitidine and decitabine are FDA approved for the treatment of both low- and high-risk patients with MDS. Clinical trials are exploring these agents as a backbone in combination with targeted therapies and immune therapies, Ai explained.
MDS and acute myeloid leukemia (AML) are biologically similar, Ai added, explaining her hopes for clinical trials for patients with AML to be extended to those with MDS.
“If we can get a label change and the same benefit for patients with MDS as the agents that have been FDA approved for AML, it’s going to be a big step for our patients,” said Ai.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Hematologic Malignancies, Ai, a physician at Levine Cancer Institute, discussed the treatment of patients with MDS.
OncLive: Please provide an overview of your presentation.
[MDS] is a pretty diverse or heterogeneous group of diseases. I focused on how to make a better diagnosis, the prognostication of this group of patients, specifically lower-risk MDS and higher-risk MDS. I also touched upon some of the clinical or practical issues that we come across.
Are any clinical trials examining the use of lenalidomide in patients with non-deletion 5q?
There are definitely trials. It has been shown that lenalidomide, or the addition of lenalidomide, can be used for patients with non-5q deletion MDS. They can definitely have a good response, though it's a little bit less than those with 5q. It's still useful in clinical practice.
What is the prevalence of other mutations and available treatments for them?
Some mutations have available targeted therapies, but none of them have been approved in the MDS world. Some of them have already been approved for patients with acute myeloid leukemia (AML). In my mind, MDS is sometimes like an earlier stage of AML. Some of the treatments can probably be used for MDS as well, though they are still [being evaluated] in clinical trials.
How has the use of hypomethylating agents evolved?
That is still our go-to regimen, because we don't have any recently approved agents. It's definitely the number one and most widely used regimen here. We also use it as a backbone. A lot of clinical trials are building upon that backbone by adding targeted therapy, monoclonal antibodies, or immune-based therapies. It's not going to go away in the field.
Can you discuss the clinical trials that are using that as the backbone?
At Levine Cancer Institute, we have a hypomethylating agent combined with a PD-1 inhibitor in the relapsed/refractory setting [for patients with] higher-risk MDS. In the field, there are different combinations, such as IDH1/2 inhibitors and BCL-2 inhibitors like venetoclax (Venclexta), in combination with hypomethylating agents. There are single-agent trials, but most of them have the hypomethylating backbone.
What is the rationale behind single-agent therapy?
This stems from the concept that if you already know something should work, people tend to build on that experience. Single agents often start in the relapsed/refractory setting. These patients have already failed 2 or 3 lines of therapy, and you’re left scratching your head in trying to get something active. Whatever potentially has a biological reason to use [is used in a] clinical trial. From a clinical trial base, MDS compared with AML is not as high on the priority list for a lot of products, even though the 2 diseases are biologically very similar. My hope is that a lot more clinical trials for AML be extended to our patients with MDS.
What is an area of research you would like to see addressed?
I definitely want to see more patient-friendly formulas of azacitidine or hypomethylating agents because patients often cannot continue their regimen—simply because of the inconvenience of the treatment. There are active trials in the oral formula that will be very interesting to see.
Is there anything else that you would like to emphasize?
It is mainly MDS awareness. It can be a deathly disease, but it has to be treated individually. You have to have an individualized plan for each [patient] because they are not the same.