More on TLS

[biopearl123]

Kmall, per your question:

https://www.haematologica.org/article/view/4719

[kmall]

Bp - Thank you for the link. Interesting read. Not being familiar with TLS before you mentioned it in a previous post, I did do a quick look into TLS, however it only mentioned TLS being associated with an increase in WBC count. What I also found didn't categorize the difference between LTLS and CTLS as cited in the abstract you provided. I know that the FDA is required to do their utmost in making approved therapies as safe as possible, but a 2% and 5% mortality rate is a chance I think most AML patients might take given their lack of alternatives.

Of interest here as well moving forward as far as Imetelstat is concerned:

"The incidence of CTLS in AML patients seems to be lower than that reported in patients with acute lymphoid leukemia (ALL) or high grade non-Hodgkin’s lymphoma (NHL),7,21–23 in whom it ranges from 11% to 25%."

There's a good chance this could be an issue as well if clinical trials of Imetelstat targeting ALL or NHL are concerned. Thoughts? - Kmall

[biopearl123]

Kmall, I have to think this or something like it is what is lurking in the background of the FDA decision to delay TELOMERE. The oncology realm is so fraught with drugs that have serious side effects (e.g., we used to call Adriamycin, “the red death” and cardio-oncology is now a recognized sub specialty as unintended side effects are a price paid for attempted life extension.) Given this however, your arguments that the short life expectancy for AML patients who have failed other therapies per TELOMERE protocol, should allow for a whole lot more flexibility from the FDA, seem very valid in the case of failed therapy in AML, what’s to lose? A few more or perhaps several months of life for patients who have no hope for a cure. At that point in the course of their disease many might choose to try a new promising combination of therapies. The FDA pattern seems to be insisting on starting with the most hopeless and the most sick to minimize the dangers of potential life shortening adverse effects. Look at the hoops Imetelstat had to jump through to get to a first line small study that finally just started after years wasted in proving the effects on patients who have failed most other therapies. This after proven CRs and PRs in some patients. The way I think of this is kind of a thought problem. (Thought problems worked for Einstein but I am no Einstein, just a guy trying to understand.) First off, progression to AML may be shown to be delayed or derailed by Imetelstat in MDS and MF studies—wouldn’t that be wonderful. But if a patient has AML and received therapy that induces a remission everyone celebrates. Only problem is the disease always recurs. So a small number (relatively speaking,) of malignant cells survive and seed the next recurrence. Is this a function of the cells being insulated somewhere where chemo can’t affect them or is it a function of the so call cancer stem cell that is resistant to therapy? Does Imetelstat or a TELOMERE like combination target the CSC? That is the question. Honestly its one that should be answered sooner than later. The FDA should know that. Regards, bp