Management of Myelodysplastic Syndromes in High-Risk Patients - Episode 7
Yazan Madanat, MD, explores toxicity and adverse events impacting treatment selection for patients with MDS.
Mikkael A. Sekeres, MD: Yazan, given that these patients tend to be older, what toxicities do you look for in patients who get azacitidine or decitabine?
Yazan Madanat, MD: That’s a great point. Just to comment on the oral decitabine, I’ve had to use it a few times, but only for convenience purposes for patients who can’t come to our infusion center on a daily basis. Despite the maybe less robust data with efficacy or survival, or the lack of a true randomized, placebo-controlled trial, convenience tends to be a big part for some of the patients who live quite a distance away from our center.
In terms of toxicity, those agents are generally quite well tolerated. That’s why they’re considered low-intensity chemotherapy when we talk to patients with AML [acute myeloid leukemia]. In general, fatigue tends to be quite a big component of it, but that’s always multifactorial, whether it’s the anemia, the disease, the therapy, or all of it contributing to fatigue. That’s something I usually talk to patients about.
For those who get subcutaneous azacitidine, they can get the local inflammatory reaction, which oftentimes can be mitigated if we switch to IV [intravenous] if it’s not very tolerable, and that can also result in some skin rashes here and there. GI [gastrointestinal] toxicity tends to be quite manageable. Whether that’s nausea, vomiting, diarrhea, constipation, or a mix of the above, they all tend to be quite mild and manageable for most patients. I’ve rarely had to switch therapy or stop or change because of those adverse effects. They’re usually managed in the outpatient setting. About 10% to 15% of patients get arthralgias. Sometimes you question whether the disease is contributing to those, or if it’s truly a drug toxicity or adverse effect. In terms of organ function, like kidneys and liver, mild liver function abnormalities can happen, but the kidneys are usually good with those agents. I’m happy with them.
I’m interested to know how you would tailor each of those therapies for a given patient in a particular setting, and some of the factors that you may weigh to select the final treatment choice.
Mikkael A. Sekeres, MD: I already revealed my cards on this a little. I go with azacitidine first because the data are just so strong supporting its use up front in higher-risk MDS [myelodysplastic syndromes]. I haven’t been won over yet by oral decitabine, just because of the approval path they took to get it based on PK [pharmacokinetics] and PD [pharmacodynamics] data. Now that I’m practicing in Miami, I have a different patient population, and I have some patients who are here from South America to initiate their therapy in Miami and then want to go back to South America for a few months, where they may not have the same availability of azacitidine. Just because they have to go back for green card reasons, I will debate using oral decitabine in those patients, but only because I have no other options.
All things being even, I go with azacitidine first. I don’t criticize people for using decitabine, because it was a study design problem that led to the decitabine study that was conducted in Europe to not have the same results as azacitidine. For lower-risk disease, I will consider truncating the courses of azacitidine and decitabine down to 5 days, or even 3 days, based on trial work that we’ve done through the MDS Clinical Research Consortium.
Transcript Edited for Clarity