Ok, one last thread with #FinalFLT3 thoughts on today’s #AML talks. #ASH20 #ASHFromHome #ASHtogether #leusm

1) First, Dr. Andrew Wei with an excellent presentation on AML M16 (sor vs placebo + chemo). No diff in EFS (primary endpt). Striking trend to improved OS in high FLT3-ITD AR in contrast to RATIFY (benefit regardless of AR).

2)What this means to me: Mido benefit = off target effect? Sor = on target? Does this mean that more potent, targeted FLT3 inhibitors more benefit. I think so.

3)Also, in sorafenib-treated responders: more suppression of pFLT3, more MRD neg CR, more FLT3-ITD neg relapses, survival after relapse higher (due to eradication of FLT3 mutation?)

4)What this means to me: Sequencing potent FLT3i upfront to eradicate FLT3 clonepts may do better even if they relapse (unless they relapse with RAS mutation?)

5) Next, Dr. Sierra with Ph3b study of mido + chemo: allowed pts >60yo, 21d mido (vs 14d), dauno or ida. 29% of pts txplted (vs. 57% in RATIFY), 26% got maintenance. No diff in response by age, sex, anthracycline but >60 yo pts with more tox, needed more dose inter/adjust.

6)Takeaways: choice of anthracycline with mido doesn’t matter, excellent activity in fit, older FLT3 mutant pts. I'll use it in a fit older pt.