Key considerations for appropriate MDS treatment selection are discussed by expert panelists.
Ryan Haumschild, PharmD, MS, MBA: Dr Weaver, I’m curious about your thoughts. I’m hearing that there are good hypomethylating agents, but sometimes people get mixed up in the community. Is there anything payers can do when there are agents being used but maybe not the most appropriate for a certain indication? Is there any type of NDC [National Drug Code] block or management that they can do to make sure patients don’t get the inappropriate type of therapy prescribed?
Jay Weaver, PharmD, MPH: There are 2 key things that come to my mind that I’ll touch on. One is that very often in cancer and chemotherapy, we use prior authorization as a tool to match the right therapy with the right person. Many times in the prior authorization process, we match the indication of the product and the disease state that they have. If they don’t qualify for something or if something is off-label, unless there’s strong evidence or NCCN [National Comprehensive Cancer Network] Guidelines or some other compendia that says, “Yes, this is a great idea,” we probably aren’t going to cover it. In some ways, that builds in. Even though it’s a utilization-management tool, it has a clinical focus to it.
Another development in this space is the advent of clinical pathways. This tool was pioneered in the 1990s with the first coming of managed care and capitated risk and other things. IDNs [integrated delivery networks] began saying, “As we track people through our system, we might come up with better ways to treat people in a more standardized fashion that are reflective of the best outcomes. Those tools have been brought forth and are being implemented within managed care organizations for certain disease states. Cancer is one of those. As we see those become more adopted, the best therapies in some cases will find themselves more prominently positioned within those care pathways. Inappropriate therapies might be left off some of those pathways.
In places where there are equivalent therapies and similar prices, we might have at that decision node either a product that is the better price or, if there are 2 choices, that decision node. Those are tools that could be leveraged, especially in a case like this, where there’s solid evidence that a product might not be the best choice.
Ryan Haumschild, PharmD, MS, MBA: Great comments. I appreciate your comment about pathways. I’m going to circle back to that in a few minutes because I want to get everyone’s thoughts on the use of pathways in this disease state. Before we do, Dr Fazal, there are many other therapies, depending on unique mutations or deletions, that can be utilized. What are the low-intensity agents used in the treatment of MDS [myelodysplastic syndrome]? What are the place of these therapies? How do luspatercept or lenalidomide play a role in the treatment algorithm?
Salman Fazal, MD: I’m glad you brought up those 2 options. I like the fact that in myelodysplastic syndrome, which in reality is a group of hematologic malignancies, we have therapy tailored to different types of myelodysplastic syndromes. The first example that you mentioned is lenalidomide. Lenalidomide was approved for treatment of myelodysplastic syndrome with chromosome 5q deletion. In that subset of patients with myelodysplastic syndrome, 60% to 70% of patients who received lenalidomide became transfusion independent by using lenalidomide, and it has a duration of response of up to 3 years. For patients with myelodysplastic syndrome with 5q, lenalidomide works quite well.
For patients who don’t have 5q deletion, lenalidomide possibly could be used. However, the response rate isn’t as good as with 5q deletion. It’s around a 26% response rate for patients who don’t have 5q deletion. It doesn’t work that well in patients who don’t have the 5q deletion. But it’s certainly an option for these patients.
The second drug that you mentioned was luspatercept, which was recently approved as well. This was studied in patients who have myelodysplastic syndrome with ring sideroblasts. That’s a subset of patients with MDS. In the study, patients who had very low-, low-, or intermediate-risk MDS with ring sideroblasts who were requiring regular transfusions were randomized to receive a placebo or luspatercept. The primary end point of the study was to look for transfusion independence for more than 8 weeks. The luspatercept arm met its primary end point, as 38% of patients became transfusion independent for more than 8 weeks. Luspatercept was approved because of this.
For the folks in the audience, luspatercept is a trap molecule that traps the TGF-β, the superfamily ligands, and by that mechanism, decreases SMAD2/3 signaling and improves the erythroid maturation. It has benefit of making these patients transfusion independent. For patients with lower-risk MDS, one goal of therapy is to make them transfusion independent. It met that end point, which led to the FDA approval for this subset of patients with MDS with ring sideroblasts.
Ryan Haumschild, PharmD, MS, MBA: Great overview of those unique patient populations. You ended on luspatercept, which is a good one. Because when I look at treatment across the country, sometimes people start with a 1 mg/kg, and they’ll do it for both indications. But as they step up, not everyone follows that perfectly. Sometimes they’ll forget about the dosing, especially people who aren’t used to treating these patients very often. Then you might have misdiagnosis or misdosing, or they might not see there have been 2 transfusions and whether they need to escalate. It can become complicated. That’s where a lot of times integrated delivery networks, like the ones that we practice at, sometimes utilize order sets and pathways to help guide clinicians who use these therapies with the optimal dosing, the right laboratory monitoring, or transfusion dependency to help guide therapy.
Transcript edited for clarity.