BSH 2023 | Promising treatment options emerging for higher-risk MDS & the value of clinical trials

So, for higher-risk MDS, I think that for many years we have continued to use azacitidine as the only drug that is available to us. Clearly whilst that was a significant advance for patients with MDS, there’s still much work to be done with only a 30% response rate with that agent as monotherapy. What I think we’re all interested to hear about will be the outcome of the VERONA study, which is combined venetoclax and azacitidine in MDS patients. There’s some concern that there may be additional toxicity for the use of venetoclax in patients with MDS and I think understanding what that data shows will really be crucial going forward as to whether venetoclax is a viable option for patients with higher-risk MDS. I guess the other thing to bear in mind is the new WHO and ICC classifications of MDS/AML, which potentially will change the landscape of available treatment options for patients with higher-risk MDS who would now be considered as having AML. Drugs that are already being looked at in the context of MDS would be CPX-351 and there are ongoing studies looking to see what the impact of CPX-351 in higher-risk MDS are. I think again, the TP53-mutated disease cohort remains our biggest challenge and although currently in the UK there isn’t an upfront study for TP53-mutated MDS, there is ENHANCE-2 and ENHANCE-3 will be opening, if not open, in some sites which enables patients with TP53-mutated AML to have access to my magrolimab. I think hopefully an agent such as magrolimab could really have some significant impact in the context of MDS and there are some data already which have shown that in earlier phase studies with magrolimab. So, I think what’s important is that having only had single agent azacitidine for many years, we’re now entering an era where we have better genomic profiling of patients, a better understanding of perhaps the way that the disease behaves, perhaps we need to understand sequencing of drugs. But I think we’re seeing more and more options coming to the fore, particularly in clinical trials. So, we need to really encourage everyone to please seek out clinical trials. So currently another study that’s open in the UK is the SELECT MDS study, which is combining tamibarotene with azacitidine, or placebo with azacitidine, for patients who have RARA positive MDS, which is about 50% of patients, and that too has shown some promising efficacy in early phase. So I think supporting clinical trials throughout the country and making sure that patients are aware and that’s where the MDS patient support group does an excellent advocacy role in letting patients know what trials and treatments are out there and making sure that patients know that they can ask to be put on trials, ask for second opinions, go somewhere where a particular trial may be open because we all acknowledge that it can be difficult to open trials across the whole country. So, I think the future is looking bright and there’s a lot of interesting data to come out.