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GERN - deaths

From GERN cc transcript... http://goo.gl/bAAW8w

So the -- there were 2 other patients in the other category that we should talk about. The first one was a patient who transformed on study to CMML and ultimately did have an off-study death to AML. And both of those events were considered unrelated to imetelstat by the investigator. Ironically, Ayalew had 2 patients with CMML that we're going to go into the study about the time that this patient developed CML and now we decided -- or he decided not to put them in but I think this is a pretty common transformation, unfortunately, in some of these patients.

The -- there was another patient in this Arm A other column who simply discontinue due to lack of response. I don't have any more data about that patient.

So now to the 2 death. One I think was a death that was certainly considered unlikely to be due or not due to imetelstat. It's a sort of unfortunate tragic story that goes along with this disease. Many patients with long-standing hepatomegaly develop portal hypertension and varices disease. And this patient had a pre-existing varices. The patient had, I believe, it was 39-day something like that into the study had a catastrophic variceal bleed, coagulation parameters were normal, the platelets counts were normal. So this patient was not considered to be a study or a trial -- an imetelstat-related death.

The other patient who was in Arm B actually tells us a lot and taught us a lot and we should talk about it. So this patient was an elderly gentleman with all -- almost all of the signs and symptoms of later-stage myelofibrosis. He came in and he was allocated, he was the 10th patient allocated to the Arm B which remember is 4 doses of imetelstat, 1 a week and then going to the Q3 weekly dosing. And as you'll see actually in some further slides, he -- at the time that he came in, he tolerated the first and second dose quite well. He had some myelosuppression on the third. At the time he came in for the fourth dose, he had a very steep fall in his neutrophils and in his platelets. By protocol at that time, we had a limit of about 30,000 platelets under which we would not treat or Dr. Tefferi would not treat -- or continue treatment. However, at the time there also was the hint that patients who had more myelosuppression might be getting a deeper response and so Dr. Tefferi thought about this. He and his colleagues thought about it and they wouldn't have been treated the patient. This patient became aplastic and subsequently died after severe -- obviously, complete myelosuppression. The patient was supported with platelets and growth factors unfortunately to no avail, the patient develops a febrile neutropenia. We assume the patient became infected and subsequently, had a CNS bleed and died. The platelet counts were very low, the white counts were very low. It was a very difficult moment for all of us. But we certainly learned that patients whose platelets were falling rapidly and also down to those levels really shouldn't be treated. This was followed by a patient who doesn't show up here but it was followed by the 22nd patient. And this was a woman who had massive hepatomegaly. Her liver was down into her pelvis. She had already had a splenectomy. She was a young women. She was dying of myelofibrosis. And she was treated and had a very a similar clinical course, a similar decision was taken because we haven't seen the effects or Dr. Tefferi hadn't seen the effects on the previous patient. And this time, however, very fortunately through I think very, very outstanding medicine, she did survive. And after prolonged myelosuppression, her platelet counts did come back, her neutrophils did come back. She eventually regained normal platelet and neutrophil counts. Her spleen shrunk up to basically a normal-size spleen or a very close to it and she has done very well. She continues on drug today. So I think that we learned that the rate of fall and also the absolute fall in particularly in platelets but also in neutrophils was a very important thing. You heard Dr. Tefferi say that this was a very potent drug and we completely agree with this. And I do think that we have used this opportunity -- unfortunate opportunity to learn about the drug and also to change a lot of the ways or some of the ways that we treat patients. I'll end up with some of those comments perhaps.