This young woman has not responded to imatinib, nilotinib, dasatinib ponatinib and was intolerant to bosutinib. Her resistance is very likely both BCR::ABL1 dependent (T315I plus M351T) and BCR::ABL1 independent. A bone marrow aspirate to look for evidence of transformation to blast crisis would be reasonable at this stage. The prospect of gaining a molecular response to asciminib is quite low, given the long term failure to response and especially the lack of response to ponatinib. However given its low toxicity and apparent availability a 3 month trial of asciminib 200 mg twice daily would be reasonable while you sort out the allograft options.
If, as expected, there is minimal molecular response to asciminib by 3 months, I would look at the best available allograft donor and proceed down that pathway. If a suitable donor cannot be identified, the only other option would be to try the combination of ponatinib and asciminib in the hope that the main driver for resistance is the T315I mutation combined with another mutation which may be responsive to the combination. This is based on in-vitro data from Michael Deininger and Chris Eide and they may be able to provide better guidance as to whether this would be a reasonable approach, what doses to use, and whether there is any clinical data to support this approach. I personally don’t see much value adding interferon to the ponatinib, although I am aware of anecdotal evidence that it can sometimes play a role in the resistance setting.
I welcome other opinions about this very challenging casa.