Re the early Mayo data, my response to a question on YMB
Posted: Tue Jul 02, 2019 4:38 am
We have talked a lot about the Mayo data in the past and lamented its apparent burial. I think we just have to accept that we will never get a final reckoning. This is a response I posted earlier today in this regard on the YMB:
Cathy, The Mayo Clinic data was the first to show actual CRs and PRs. This data was published in the New England Journal, the most prestigious medical journal in the world. There were also CIs (clinical improvement patients) but the FDA required all patients who were not CR and PRs to be dropped due to the nutso hold due to elevated liver enzymes none of which met Hy's criterion for liver toxicity as far as I know. Also the patient numbers were small and as Scarlett said were "all over the place" in other words multiple different DIPPs criterion, basically all comers even a few AML patients who apparently showed a response. A lot of the data was published (see Geron's web site) but lots of other sub rosa stuff happened including an apparent freezing out of Dr T and a subsequent Mayo patent filing which I suspect was not done with the company's blessing but that's just conjecture. The structure of the study would not have been a path to approval. Nonetheless, seeing some survival data would have been welcome and we really don't know how long responses lasted or what other therapies were brought to bear. Yes there is valid criticism but little to be gained by looking at this study which was a hodgepodge anyway. As Dr. Raza said companies design studies to lead to approval if they can and the Mayo study wasn't it. We should move away from chasing this lost and potentially uninterpretable data. Also, Dr. T gave some patients a weekly injection of Imetelstat which led to profound cytopenias (I am not sure if they reversed or not, does anyone remember?) and the doses. The current doses schedule for existing and future studies have been modified in a major way. While I would have been very interested in a final reckoning from the Mayo, I think we will never get it and should move on to look carefully and more modern study design and dosing schedules. Regards, bp
Cathy, The Mayo Clinic data was the first to show actual CRs and PRs. This data was published in the New England Journal, the most prestigious medical journal in the world. There were also CIs (clinical improvement patients) but the FDA required all patients who were not CR and PRs to be dropped due to the nutso hold due to elevated liver enzymes none of which met Hy's criterion for liver toxicity as far as I know. Also the patient numbers were small and as Scarlett said were "all over the place" in other words multiple different DIPPs criterion, basically all comers even a few AML patients who apparently showed a response. A lot of the data was published (see Geron's web site) but lots of other sub rosa stuff happened including an apparent freezing out of Dr T and a subsequent Mayo patent filing which I suspect was not done with the company's blessing but that's just conjecture. The structure of the study would not have been a path to approval. Nonetheless, seeing some survival data would have been welcome and we really don't know how long responses lasted or what other therapies were brought to bear. Yes there is valid criticism but little to be gained by looking at this study which was a hodgepodge anyway. As Dr. Raza said companies design studies to lead to approval if they can and the Mayo study wasn't it. We should move away from chasing this lost and potentially uninterpretable data. Also, Dr. T gave some patients a weekly injection of Imetelstat which led to profound cytopenias (I am not sure if they reversed or not, does anyone remember?) and the doses. The current doses schedule for existing and future studies have been modified in a major way. While I would have been very interested in a final reckoning from the Mayo, I think we will never get it and should move on to look carefully and more modern study design and dosing schedules. Regards, bp