Sep 3, 2026 · 15 min · 8 segments
PARADIGM is finally published, so we have more details from this study presented at ASH about HMA/Ven vs. Intensive Chemo if fit patients with AML. Daraxonrasib looks like a promising drug for…
John BazarHost
So they could be less than 60, as long as they did not have those types of leukemias that we think we can cure with just chemotherapy.
And if you're over 60, you had to be, you know, fit enough for 7 plus 3 or CPX351 because that's the intensive chemo arm at 7 plus 3 or CPX351.
Um, the folks randomized to intensive chemo, you know, they did, um, they did a bone marrow biopsy around day 28, days 21 to 35 or so, and they could do reinduction with either 5 plus 2, if you had 7 plus 3, so the same dose of your anthracycline, either DONO 60 or Ida 12 and cytarabine, the 200 per meter square of cytarabine.
in a five plus two approach or cpx on just days one and two um in re-induction um or a's event can kind of continuously here what is i think really key to hone in on is the primary endpoint of this study is event free survival and events can be whatever we say they are it's not necessarily death although in this case it does include death but it also includes uh progressive disease Persistent disease prompting therapy change, relapse, hospice, death, as determined by the investigator.
So you can imagine a scenario where somebody gets intensive chemo or they're getting A's of N, and that first bone marrow, they have a good response.
Well, you might not change therapy, but let's say they don't have much of a response.
You might wanna change therapy, And you can see that maybe you're more likely to change therapy for intensive chemo to a different intensive chemo regimen rather than continuing A's of N, which we think is more of a kind of a slow and steady path to treatment.
It's a phase two study, so it's not necessarily designed to unseat the current standard of care, but it was designed to have 85% power to have a hazard ratio of 0.635 with a one-sided alpha of 0.1. which is a lot, so you know, phase one study, the median fall period is about 22 months.
However, more than half the people in the study did have AML with myelodysplastic relay changes, which probably explains for the CPX351 benefit.
About 13% total had favorable risk based on the European Leukemia Net Favorable Risk AML.
Again, we're not including folks that have core binding factor leukemias or NPM1 if they're less than 60.
If they're over 60, again, no core binding factors, but if you're NPM1 positive, you were there.
So all those folks, probably all those folks that are favorable risk might have to be NPM1 positive over the age of 60. which is about 9% of the population.
So they could be less than 60, as long as they did not have those types of leukemias that we think we can cure with just chemotherapy.
And if you're over 60, you had to be, you know, fit enough for 7 plus 3 or CPX351 because that's the intensive chemo arm at 7 plus 3 or CPX351.
Um, the folks randomized to intensive chemo, you know, they did, um, they did a bone marrow biopsy around day 28, days 21 to 35 or so, and they could do reinduction with either 5 plus 2, if you had 7 plus 3, so the same dose of your anthracycline, either DONO 60 or Ida 12 and cytarabine, the 200 per meter square of cytarabine.
in a five plus two approach or cpx on just days one and two um in re-induction um or a's event can kind of continuously here what is i think really key to hone in on is the primary endpoint of this study is event free survival and events can be whatever we say they are it's not necessarily death although in this case it does include death but it also includes uh progressive disease Persistent disease prompting therapy change, relapse, hospice, death, as determined by the investigator.
So you can imagine a scenario where somebody gets intensive chemo or they're getting A's of N, and that first bone marrow, they have a good response.
Well, you might not change therapy, but let's say they don't have much of a response.
You might wanna change therapy, And you can see that maybe you're more likely to change therapy for intensive chemo to a different intensive chemo regimen rather than continuing A's of N, which we think is more of a kind of a slow and steady path to treatment.
It's a phase two study, so it's not necessarily designed to unseat the current standard of care, but it was designed to have 85% power to have a hazard ratio of 0.635 with a one-sided alpha of 0.1. which is a lot, so you know, phase one study, the median fall period is about 22 months.
However, more than half the people in the study did have AML with myelodysplastic relay changes, which probably explains for the CPX351 benefit.
About 13% total had favorable risk based on the European Leukemia Net Favorable Risk AML.
Again, we're not including folks that have core binding factor leukemias or NPM1 if they're less than 60.
If they're over 60, again, no core binding factors, but if you're NPM1 positive, you were there.
So all those folks, probably all those folks that are favorable risk might have to be NPM1 positive over the age of 60. which is about 9% of the population.
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