Revisiting the basic question:Where are the Imetelstat patients?

[biopearl123]

Given the Moffett is a major center for MF and clearly contributing to IMpact, the recent EHA presentation created some consternation re “new era” OS which we analyzed like crazy I just want to re pose the question: where are post 2019 Imetelstat patients? Here is Claude: (and yes we have discussed this before.) I have been interested in the long plateau on the KM curve with lots of censor marks and not a single death from 12 months to 30 months, not one death? Take a look for yourself. This may represent a time when newer Rux therapies introduced or patients entered a trial. Here’s Claude:

good. this actually helps.

the key sentence from the ASCO coverage of that abstract is:

“earlier switch to next-line JAKi or clinical trial enrollment”

that wording is extremely revealing.

it means:

the registry did track patients who moved beyond rux failure into subsequent therapies and trials as part of the treatment landscape.

that argues against automatic censoring at trial entry.

if trial entry itself caused censoring, they usually would phrase it as:

“censored at subsequent investigational therapy.”

instead they discuss trial enrollment as part of the explanatory biology of improved OS.

that strongly suggests:

IMpact patients are probably in there.

which answers your question:

where are they?

likely embedded in the post-2019 cohort.

not hidden.

not censored off for purity.

just blended into the survival curve.

that has major implications:

the 39.8-month post-2019 OS is likely not:

BAT-alone OS

it’s more like:

BAT + newer JAKi + clinical trial ecosystem + occasional transplant

including at least some Imetelstat exposure.

so your original suspicion evolves:

not “they censored imetelstat to hide IMpact.”

more likely:

they didn’t censor it, which contaminates the modern comparator upward.

that may actually be the bigger issue.

[seedylemon]

BP:
I'm confused. Are you suggesting that the newer Rux therapies have corrupted IMpact?

[biopearl123]

Seedylemon, no, I am not saying that at all. I think the study BAT is as insulated at it can be. But it may be affected by treatments that preceded enrollment into Impact e.g. newer JAKi's, changes in pre randomization use of Rux, (or randomization into a study). I think Geron has acknowledged the newer JAKi part of this. What I am struggling to understand is how a major MF treatment center clearly involved in Impact tracks patients who are post Rux failure. Are they somehow contributing to the post 2019 mOS determinations (which I am thinking is possible) but asking if that data is allowed to be censored since it's not on the approved list like the other "next therapies" in Dr. K's abstract. My point is only that I hope I am correct on this, that censored data (even if we don't know the explanation as to why that data is censored) can still contribute to mOS determination. I am no statistician and I could be way wrong on this. For example, in previous studies, bone marrow transplant patients were censored since that therapy clearly distinguished itself in its ability to prolong survival and would mess up the stats that looked at everything else but.