Gail Roboz, MD: if you think back to the days of what was happening with the initial Len data, Lenalidomide in 5Q patients, I mean those hemoglobins were from seven to 14. I mean that was, I think exceptional and then there was about a 25% or so benefit for some patients who, in the absence of 5Q, but I'm thinking Azra, do you want to take us back in time to when that was all new and what do we do now with Len, however many you know, 100 years later and what can we do? Is there anything that we can do to optimize the use of that drug for our transfusion dependent patients?

Azra Raza, MD: Thank you Gail. As you might remember, Lenalidomide days, we were very excited actually about it's activity also in the non-ablation 5Q patients. And we published together the vote of something like 214 patients where it was 26% transfusion independence, 43% response rate of non-ablation 5Q. But here I want to talk for a minute about the deletion 5Q also because we have been limited to starting Lenalidomide in these deletion 5Q patients once they become transfusion dependent. But I think one of the reasons studies clearly have been very exciting, showing that if you begin it early before patients become transfusion dependent but they have dropped their hemoglobin below 12 grams and you start like low dose Lenalidomide at 5 milligrams continuously, it seems to be really benefiting patients in terms of trying to transfusion dependence is something like 75 months versus 30 months per patient, individuals who got the placebo. These are deletion 5Q patients with anemia not yet transfusion dependent. Build time to transfusion dependency is increased and I think in addition to that, the duration of transfusion independence might also be much better for these people. I think Lenalidomide number one, has a role to play even in deletion 5Q patients starting it early and in non-deletion 5Q, one has to balance the side effects, the toxicities, the mild separation. All those things with the expected benefit of 26% which was proved in a placebo-controlled phase three trial. But, with the duration of response in about eight months. And so, is it worth it or not? No.

Gail Roboz, MD: OK, and James, what about the patient? I think we all have this patient about three times a week. So yeah, there's a 5Q. But there are 23 other commas and semicolons and numbers next to the 5Q. Are we Lenalidomiding, if that's a verb, that patient?

James Foran, MD: Yeah, I have. I think we all have also because we don't have that many options and I like to do that before other systemic therapy like a hypomethylating agent when people do become symptomatic with their low-grade disease or their lower risk disease. Yeah, the response rates are lower if you have more abnormalities or if the blast count is higher. There is a legitimate rule. You just have to account for the neutrofils in the platelets because there is mild suppression. I think it's OK to do and it seemed to benefit.

Gail Roboz, MD: And Rami, do you still think, so back in the day, if you really have an isolated 5Q, we actually discuss this so frequently that you might have like a real dip in the sort of cytopenia if you knew you might notice a real dip that you kind of have to watch the patients carefully and not just give them a pack of pills and say come back next month. But actually, watch them and that might even be a sign of efficacy, so don't necessarily run away from the therapy if you see initially worse cytopenia's. Do you think that's still true? That's what we used to say.

Rami Komrokji, MD: Absolutely, and I have to say that it's still, 20 years later, that that's sometimes one of the most common things that I see that the treatment is stopped and never even tried again. So, I think you know, published this that the depth of cytopenia and del5Q correlated with the response while necessarily in non del5Q. So, I actually tell the patients this very clearly and I write for them and usually it's deducted initially sending it to the doctor. I would say like, we need to check your counts every week in the first eight weeks. By three weeks, you are going to dip down if the platelets go below this and you need to this you have to stop, it's normal, you stop for three weeks and then you need to readjust the doses. It's really the first month or two, either because of site cytopenia or rash were in del5Q. I think many patients unfortunately get stopped early on unnecessarily. If you just get through that, then they will have the count. The platelets will never go back to the normal days. They will always hover in the lower 100's maybe. But that's OK because then I exactly mentioned. You go from eight to like 13. So, it's very crucial what you're mentioning about the cytopenia up front. It's very predicted, manageable, but it's like basically you are getting rid probably of the common myeloids that carry del5Q and waiting for some recovery of the 5Q sense.

Gail Roboz, MD: Right.

Azra Raza, MD: Rami, that is only for the deletion 5Q. What about, what is your thinking about the non-deletion 5Q?

Rami Komrokji, MD: Right, so in the non del5Q, like first when I use it is just patients that are purely anemic. There is some neutropenia or thrombocytopenia, it's both ways. First, the responses are less in my experience if they have cytopenia's, even if they are mild. And obviously like you know, the cytopenia in non del5Q is not as much. I use it in purely anemic patients, and I use usually before hypomethaning agents if I'm going to use it. We published on the sequence, if we used it after hypomethaning agents in our experience and again, this is retrospective, the responses were like 15% only. We recently published some data in combination with agents, while we see a little bit higher response. This is the group study and a little bit longer in duration that you mentioned because I always struggled as you mentioned, it's like what is the benefit of only six months to independency. What's that got, you know. So, if I'm doing it non del5Q, I just do it in anemic patients after and I may consider combining it with ESA and if in three months there is no, three to four month no response, I will just abandon that.

Gail Roboz, MD: So right before you said that I was going to say to Amy, hey, do you believe Rami data on doubling down and putting in an ESA plus the lens. I'll ask you anyways, is that something that you would do to to try to give an extra kick, would you combine an ESA and Lenalidomide for selective patient?

Amy DeZern, M.D., M.H.S.: Yes, I actually do. Only non del5Q, I don't do it in the 5Q minus syndrome patients but the B290605, the number of that through the clinical trials network clearly showed that there is a benefit of the combination and as James alluded to earlier, I certainly don't continue them ad nauseum. But the combination early on, I try to get that extra kick in some patients.

Gail Roboz, MD: And before I have an attempt at an artful segue to high risk, I want to give James a minute to talk for a second about Eltrombopag, which is a not specifically approved for MDS agent, but something that is with some data and with lot of discussion for some of our especially lower risk patients. Do you want to give us a brief tour of that?

James Foran, MD: Yeah, I'll be quick, I just want to make the point that anemia is a big problem but for a minority of patients, thrombocytopenia is a big problem and there are now two small, randomized studies showing that Eltrombopag in lower risk patients can have a platelet response that can be meaningful. So, we've used that for some patients based off, it's off label, it's not always to get but I've seen many patients get a meaningful platelet response and come out of a transfusion situation and keep levels of 30 or 50 or higher with Eltrombopag and I think it's mostly safe in low risk MDS to do that. So, I wanted to make that point also.

Gail Roboz, MD: No, I appreciate your bringing it up and I think it's great to be aware of those data.

Transcript edited for clarity.