Be still my heart, you know I love me some drug resistance talks! Session 604 was! Some highlights. THREAD. #ASH20 #ASHFromHome #ASHtogether #leusm #ImaHemeDork.

1)First up, on target resistance wins again! @JianXuLab with an unbiased saturation variant library phenotypic screen for IDH1 and IDH2 inhibitor resistance. Results validated in pts = clinically relevant IDH1/2i resistance mutations.

2)Next up, from Sunil Joshi @OHSUKnight -NRAS mutations and gatekeeper F691 mutations evolve with gilteritinib resistance in an in vitro resistance model.

3) @jaltmanmd and @yazan_14 show TKI pre-treated pts respond to gilteritinib but NRAS/PTPN11 associated with decreased response/survival.

4)BAX mutations? Who knew they could be so interesting?! Drs. Moujalled and Wei:
Loss of function BAX mutations associated with resistance to venetoclax. Loss of BAX but not BAK confers resistance to BCL2i/MCLi combination.

5)BAX again…Dr. Blombery reports BAX mutations in the myeloid compartment of CLL pts treated with long-term venetoclax. Mutations co-occur in cells with CHIP mutations. Pts can also have co-existent BCL2 but not BAX mutations in the CLL cells.

Great first day! @ASH_hematology #ASH20 See you all tomorrow!