Dear Nobuko,

Your teenager patient was initially diagnosed in 2017.

If no information about the correct use of the medication had been given, I would think of poor adherence. This transcript curve resembles poor compliance usually seen in the AYA population, with ups and downs.

With these thoughts. I would consider BMT.

Best regards,
Acy Quixada (Brazil)

HI Nobuko
Tough case
I would re-screen for ABL kinase mutations as this could explain the failure to asciminib.
Unless there are barriers to treatment or concern over specific AEs ponatinib would be reasonable at 45 mg to start to try to salvage but this then raises the SCT agenda higher as longer term ponatinib may carry greater risk. As Jeff mentioned we don't have much sense with the sequential response estimate but i do agree with the approach of 'lower risk, possibly higher yield' asciminib first...
Best
Mike

there is little data on PON after ASC, but even with a response, I would not be confident about durability
I would allograft ASAP before he blasts off

Hi.
I want to have your thoughts on the same case we discussed a while ago. The patient is now 20 yo. He has failed with three TKIs, started asciminib in Apr 2022, and maintained the PCR in 0.1-0.2%IS range but attained MMR only a few times. I previously said he was on 40 mg BID, but actually, he was on 80 mg QD.
He came back for follow up recently and PCR went up to 2%. I asked our BMT team to do donor search again and now, they have an unrelated donor with 9/10 match. (Previously, there was only haplo.) I have thought about switching asciminib to ponatinib, but I think the same thing will likely happen; he will respond, but will lose molecular remission after a while.

With a better donor option, I am thinking about taking him to HSCT now.
I would appreciate your suggestions

Nobuko Hijiya
Columbia University, NYC

Hi Nobuko,

Very difficult case. It looks like he will not sustain a good molecular response to asciminib but I would probably watch for a few more months to be sure. If he is losing response to asciminib, which looks likely, and given the less than ideal donor, I would be thinking about ponatinib (45 mg/day with reduction to 15mg/day if/when he achieves MR2) as a last chance before considering the transplant option. Before stopping the asciminib it would be important to screen for kinase domain and myristoyl site mutations. Any single mutation should not represent a problem for ponatinib but if he has compound mutations, ponatinib may not be a good option – depending on the actual mutations.

Cheers - Tim

Dear Nobuko,

I suggest to maintain him on asciminb, simplify at 80mg QD and from time to time if fluctuation stable, ask for KD mutation analysis.

Best regards,

Delphine Rea