First thought- asciminib does not have a strong/proven track record in advanced phase disease. I think it is good at treating BCR-ABL driven disease and subverting mutations. I worry about myeloid sarcoma. I would look carefully in the marrow and elsewhere, broad sequencing, etc so you can make a solid decision about induction but it sounds necessary.

Asciminib+chemotherapy would probably be out of bounds- never tested. Asciminib single agent, no track record really for the sarcoma component. So it almost makes it moot and thinking more of a myeloid induction, as t315i disease resistant to PON likely has multiple mutations ('t315i plus').

If you block the sarcoma out of your mind it makes asciminib more attractive, but again without a track record in myeloid blast phase and relying on it single agent (as combo with chemo likely out of bounds for compassionate use) pre transplant may be false hope of 'MRD' or disease control pre transplant.

I was hoping to get your thoughts on a new patient. 52yo, diagnosed with CML in 2016, intermittently compliant with imatinib, started on dasatinib mid 2019 due to lack of response (but hard to evaluate adherence from notes). Late 2019/early 2020 she develops a myeloid sarcoma, also a T315I mutation. She is started on ponatinib 30 mg. Initially has a hematologic response, chloroma goes away (on exam at least, refused radiation). She’s now lost hematologic response, WBC in the 50’s, PCR >50%, ponatinib then increased to 40 mg (not sure if that’s a typo from notes and she’s really on 45mg). Anyway, assuming compliance with ponatinib… I was thinking of getting her asciminib through the expanded access program.

In theory she would be a transplant candidate as she is 52 and in good health but socially has a lot of issues making this challenging…

If she does agree to a transplant- would you give her induction chemo? (with asciminib?) or try asciminib alone? Supposedly marrow done a week ago is consistent with chronic phase CML. I don’t have recent image to confirm that there is no myeloid sarcoma elsewhere…

If I don’t give her induction- do you think asciminib monotherapy is appropriate? There are some studies supporting combination of this drug with other TKIs, but clearly this is not established in clinical practice…