Luspatercept: An Erythroid Maturation Agent in MDS

EP: 1.Myelodysplastic Syndrome Diagnosis and Risk Assessment

EP: 2.Clinical Considerations in the Diagnosis of Patients with MDS

EP: 3.The Impact of Mutational Status on Treatment Considerations for MDS

EP: 4.Staging Models in Diagnosis and Risk Assessment of MDS

EP: 5.Individualized Treatment for MDS

EP: 6.Guidelines for the Treatment of MDS

EP: 7.ESA Use in the Treatment of MDS

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EP: 8.Luspatercept: An Erythroid Maturation Agent in MDS

EP: 9.Treatment of Transfusion Dependent MDS

EP: 10.Use of HMAs for the Treatment of MDS

EP: 11.HMAs in High-Risk MDS

EP: 12.Role of Transplant in MDS

EP: 13.Treatment in Older Patients with High-Risk MDS

EP: 14.Emerging Role of Venetoclax in the Treatment of MDS

EP: 15.Promising Data for Pevonedistat in High-Risk MDS

EP: 16.Unmet Needs in High-Risk MDS

Gail Roboz, MD: Luspatercept was approved which has a different mechanism of action and we think is actually perhaps of specific benefit in that RARS, the group, plus or minus NS of 3B1 mutation but I think lots of us feel very positive when we see the RARS together with MS of 3B1 and I'm wondering, Rami, if you wouldn't just want to comment quickly like how, how this new agent has changed what you're ESA algorithm is?

Rami Komrokji, MD: Absolutely, so obviously, the exciting thing about Luspatercept is that it was the first drug we got approved and for MDS so that by itself is a milestone for all the people that have worked on this. The drug, you know, is now described as a first class in what we call the metatoric matulating agent because the mechanism of action, it works a little bit more on the terminal differentiation rather theoretically therefore it's stimulating agents work an earlier step. The Luspatercept got approved in patients with ring sideroblasts which as we mentioned enriched with SF3B1. The study was done in patients that are transfusion dependent. We actually looked at the data before, like we started those classified agents with other drugs. But with the Luspatercept, the responses were not really peculiar of ring sideroblasts nor to patients with SF3B1 but that's where the highest responses were seen and that's where we moved into. From the ring sideroblasts study adversely, the drug led to red blood cell transfusion independency. My take on it obviously when you look at the data, the real benefit of transfusion independency was in patients that were not having a transfusion dependent. So once patients get into the six to eight units every other month, those patients may benefit a little bit in transfusion reduction but really not transfusion independency. So, in my algorithm now, if patients have that, adequate trial as very well discard of ESA and we are moving to the next step, I do ask, do they have ring sideroblasts and if they do, I try to introduce it earlier a little bit. Before the patients are heavily transfusion dependent. The drug is given once every three weeks. It's very well tolerable. There are some side effects. We have had a couple of patients that had to come off but in general very well tolerated in injection subcutaneous every three weeks. Important to do the escalated per the package insert and there no doubt that the responses in patients that are not transfusion dependent are really in the middle of study. If patients were not having a transfusion dependent, it exceeds 50%. The drug is being looked at in combination. It's being looked at to be moved up front in comparison to ESA's. I think hopefully we will be able to extend the benefit of Luspatercept beyond the ring sideroblasts patients at this point. It's definitely one more option that we never had before.

Gail Roboz, MD: I'm totally curious whether anybody's going to be able to fish out any data that says that the osteoporosis of some these, if you imagine, some of the MDS patients who are like little, tiny ladies who you know are osteoporotic and they're getting transfusions. I've thought that would be so nice if that mechanism of action could actually help. That as well, I think that became a secondary goal because they got derailed away from that. But wouldn't that be nice to be able to say and you don't have to your, as much calcium. But I think that you know, we saw a long, long time ago the I think, most dramatic affects I think that I've seen so far in my career on red cells was what we saw with Lenalidomide in the 5Q patients. I think that we all have seen benefits from ESA's. I think it's great to have Luspatercept on the block and I got to tell you, I felt the same way that finally we have some MDS drugs to play with too.

Transcript edited for clarity.