Ira Zackon, MD, The US Oncology Network, The Woodlands, TX, discussed his retrospective study which aimed to understand patient characteristics, treatment patterns, and OS in those with higher-risk MDS treated in the community oncology setting. These findings were presented at the 64^th ASH Annual Meeting in New Orleans, LA.

Transcript:

I'm Dr Ira Zackon. I've been a practicing hematologist for well over 30 years within the US Oncology Network, and I am a senior medical director with Ontada, which is our data real-world research and evidence leveraging our EHR, the electronic health record, we use across the US Oncology Network. It's a large database rich in research questions.

Our particular abstract here, it was in the space of myelodysplastic syndromes [MDS]. MDS is a disease primarily in the older age group and has always been challenging in terms of outcomes. We've had very limited therapy options over time. This was a retrospective study that was really descriptional on patterns of care for a decade, going back to 2011 through 2021, so really reflective of that decade of the management of these patients.

In retrospective research, of course, we see the real world. These are patients being treated in a community setting, and we know prospective trials which lead to the therapies that come through FDA approval to treat our patients, our more selected population, and the real world is where we can really learn what's really going on out there in terms of treatment patterns and outcomes, which was the primary focus of this trial.

To our knowledge, this is the largest aggregate retrospective study in the MDS population. We had over 2,700 patients for this dataset, and the median age of the patients was 75, with 40% women and 60% men. That is reflective of this disease space in the real world. That's important when we're looking at this data.

What we saw, MDS has different prognostic subgroups. We say there's low risk, and then we have what we might consider in aggregate high risk using the revised IPSS, which is a prognostic score that integrates the degree of lowering of the blood counts, as well as the cytogenetics, so the gene mutation spectrum, using classic cytogenetics during this time period.

We focused primarily on those patients who had what we would consider then not low-risk in the R-IPSS, that's intermediate, high, and very high risk. In that population, first thing that we saw was that we were looking at patients, what did they receive in first-line therapy? First, we saw that about 75% of the patients did go on to first-line therapy. First, we see a gap of about 25% of patients that in our EHR documentation, we don't see that they received a treatment.

Now, when we're dealing with retrospective EHR-based data, we realize that there can be some gaps in that data. It is possible that some of these patients may have been treated outside of the US Oncology Network, whether on a clinical trial or on an active therapy. Some of the patients could go to an allogeneic bone marrow or stem cell transplant. We did look at that. Only about 10% of this patient population went to transplant, which is typically used in patients who are closer to an acute myeloid leukemia, which is how these diseases can evolve. But not surprisingly in this age population, a smaller percentage or small minority would go to transplant.

But in the real world, there are a variety of reasons that some of these patients may not get onto treatment, whether it does to their other health status, comorbidities, individual choice and decisions, and of course increasing appreciation of social determinants of health and some of the barriers perhaps to access to care.

Then when we look at the patients then, the majority who were treated, hypomethylation agents, such as azacitidine or decitabine, have really been the primary therapy that we've had to treat more advanced MDS. The majority of these patients received azacitidine, approximately three-quarters. A smaller percentage received decitabine, and then a much smaller percentage received an oral decitabine agent, which is only more recently used, or lenalidomide, which is primarily used in the low-risk group. So, this is primarily then reflective of what we had available as hypomethylation agents.

I think the next important point that we learned was that we know when we treat patients with hypomethylating agents, it's important to keep them on at least for 4 monthly cycles before you make a judgment on the impact of that. Then on those that are responding and having an adequate tolerance, you will have continuous therapy.

Well, what we saw across these groups was that the median duration on a hypomethylating agent was only about 4.8 months, so a little bit over 4 months. Even the outliers are generally less than a year from that median. So, it's really telling us the limited impact of these therapies in terms of whether efficacy or patients staying on therapy.

Then the next point in the patient journey of treatment is, well, what happens when they come off of an HMA? Do they go on to a second-line therapy? Here, the vast majority did not get onto a second-line therapy, over 80% in this group. That partly reflects that we did not have really a lot of other options. In fact, many ways, we still do not have a lot of options to treat these patients.

Again, the caveat, a small percentage would be eligible to go for an allogeneic stem cell transplant, and some of these patients may have been treated outside of our database. But the majority I think we would understand that they didn't go onto a second therapy, even more so than getting onto first-line therapy.

When we look at the overall survival data with this patient population, first, it does show some validation of the R-IPSS prognostic scoring system so that we can see the clear subsets of patients in terms of their overall survival. For example, when you look at the low-risk population, their median overall survival was 67 months, so well over 5 years towards 6 years, and, of course, with some of that population 7, 8, or longer years. That's the more favorable subgroup.

But when we get into the intermediate or high or very high risk or an aggregate, what we did in our study was just group these for purposes of analysis into a high-risk MDS, that their overall survival was just under 2 years. Again, if you were in the very high risk, that was only about 12 months. If you were intermediate, which is probably the majority of patients in that space, it was about 20 months.

This study is really descriptive. It's helping to really define a really important ongoing need to really make more of an impact in MDS patients. Again, as we said, this is primarily a disease of patients who are older, and so there's a clear need for new therapies in this space to really start to impact the lives of our patients more.