Ryan Haumschild, PharmD, MS, MBA: Dr Fazal, when we’re looking at patients, there aren’t a ton of medication therapies, but there are IV [intravenous] and oral therapies. Payers are looking at it from a medical benefit and pharmacy benefit, and there’s a lot of discussion. But when you’re thinking about the patient journey and what’s best for the patient, how do you stratify patients and say, “This person might be more ideal for an oral therapy—they’ve got good adherence,” or “This patient hasn’t done well on their chronic medications. They aren’t staying compliant. I want them to come into the clinic. I want them to sit in a chair and know they’re getting the drug.” How do you stratify patients when you think about your treatment-planning process? When should patients be transitioned from IV hypomethylating agents [HMAs] to potentially an oral if it’s available?

Salman Fazal, MD: When you think about patients with myelodysplastic syndrome [MDS], because we’re dealing with the older patient population and there are transportation issues, I’m always more interested in using oral therapies, so they don’t have to come to the office or the cancer center to get the infusion. We’re living in an environment with limited resources, so using the infusion centers for these patients is sometimes also a burden. If everything is the same, I prefer using oral therapy.

However, one other challenge with oral therapy is that there’s always a delay in getting the patient started on therapy. Sometimes we’d like to start the patient therapy right away. If there’s a delay in getting the insurance coverage or co-pay assistance, that sometimes adds to the time before a patient could be started on therapy. That’s frequently one of the major reasons that, as a clinician, if there’s an alternative IV version, we’d start with the IV version and then consider switching to oral therapy.

One other thing that you mentioned about the oral therapy is compliance. However, when we think about compliance, a medication that has to be taken daily for the entire month is different from a medication the patient has to take for only 5 days a month or for 5 days every 28-day cycle. There’s a little room there. I don’t feel that worried about the compliance for a patient who has to take the medication only 5 days. They will take it for just those days.

One other challenge with the oral therapy that I like to highlight is dose modifications. If I start the patient on a certain dose, and I decide I’m going to cut down the dose for the next cycle, sometimes you have to order the different strength of the medication, which always delays that. Fortunately, with oral decitabine, the dosing is so easy that it isn’t an issue. But with other oral medications, that could be a challenge. As a clinician, some of these things come into my mind to decide whether I’d use the IV version or the oral therapy for any therapy. But if a patient is on IV therapy, such as IV decitabine, for all practical reasons, if they’re covered and there are no issues, I’d certainly prefer using oral decitabine.

Ryan Haumschild, PharmD, MS, MBA: I appreciate you walking us through that process. It’s always interesting to see that real-world application of the different agents and how you think about it for your patients. Before we end, I want to hear about the opportunities that exist for oral agents in MDS. Dr Zeidan, what are some of the challenges to adherence for both IV and oral agents? What could you improve in oral agents? One thing you mentioned earlier is that an oral agent is just as unsafe or worrisome as an IV product. We need to make sure we treat it the same way. What are some of those opportunities that exist? What are some of the challenges to adherence with both types of therapies?

Amer Zeidan, MBBS, MHS: This is a great question because there are 2 important areas. One of them is the initiation of HMA therapy. We know that those therapies improve survival, improve quality of life, and provide significant benefits to patients with high-risk MDS. However, when you look at the population within the United States, we’ve done multiple studies on that, and more than half of the patients with high-risk MDS in the United States still aren’t getting any treatment. You’re talking about a developed country with a lot of resources. They’re being treated with only best supportive care, transfusions. That’s sad because it deprives those patients from the potential benefit of improving their quality of life or potentially survival.

When you drill more into this, from my clinical experience, we have patients who refuse treatment because of the reasons we mentioned earlier: they don’t have someone to bring them in for 7 days every month, every day. You have to remember that the patient will often have to drive 1 or 2 hours, park, pay for parking, and wait in a waiting room for sometimes an hour, depending on how efficient your cancer center is. They’ll get the infusion, and then they’ll have to go back.

It isn’t like going for an injection. Many times, it’s a full-day affair to get a day of azacitidine or decitabine. Imagine doing this for 7 days every month without being able to cure what the patient has, while telling the patient, “You have to continue on this as long as you’re responding, possibly for the rest of your life.” When patients hear about all this, and they know that this is a disease you’ll often end up dying from anyway, many will decline HMAs. We can see it from a patient perspective. Making the delivery of those drugs to those patients as easy as possible is important. The introduction of an oral version certainly can affect that.

The other part that Dr Weaver alluded to is that significant differences in coverage of those drugs has also been a problem in the US system. I never understood why it was designed this way. But with many things that you give in the doctor’s office, many patients don’t end up with a significant co-pay. When you give azacitidine or decitabine in the infusion clinic under Part B, many patients don’t have any significant co-pay. But if you want to give them an oral version, and it goes under Part D, sometimes you can get hefty co-pays. It’s sad when a patient says, “I want to do the oral drug, but I can’t afford this co-pay. I’m willing to come in and do the 7 days of injection, although it’s much worse for my quality of life because I can’t afford it.”

I’m hopeful this is going to be fixed soon for the oral vs injectable variety for anticancer drugs. Having oral agents improving the cost-sharing component of patients can go a long way in improving the adherence and uptake of these drugs. Ultimately, as we’ll talk about in the next section, hopefully even better therapies could significantly alter the natural history of patients with MDS as we go into the combination era.

Transcript edited for clarity.