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A 19 yo on asciminib as 4L, new updates

Nobuko Hijiya
Topic Author

1 year 1 month ago - 1 year 1 month ago #1930 by Nobuko Hijiya

A 19 yo on asciminib as 4L was created by Nobuko Hijiya

The patient is a 19 yo male. He was initially diagnosed in 2017. He came to us from another center after he failed imatinib, dasatinib and nilotinib. There is no doubt about his compliance. He has responded to each TKI initially, then, the level went up. He did not have TKD mutations. When he was referred to our BMT team, I suggested asciminib as he was18 yo. (Asciminib has not been approved for children.) He started standard dose 40 mg BID in April 2022 and achieved molecular remission. He achieved MR3 in 4 months but there are some up and downs up to 0.5%4/12/22 10.3% (prior to asciminib)5/31/22 3.4%8/19/22 0.13%11/18/22 0.039% (MR3)3/9/23 0.065%6/27/23 0.58% (lost MR3)7/10/23 0.375%7/28/23 0.098% (regained MR3)8/29/23 0.028% (the lowest so far)9/25/23 0.108%10/25/23 0.21%The best donor option is haplo. What do you recommend?
I appreciate your thoughts.
Nobuko

Nobuko Hijiya, MD
Pediatric Oncology
Columbia University Irving Medical Center

Last edit: 1 year 1 month ago by arlene.

Delphine Rea
Topic Author

1 year 1 month ago - 1 year 1 month ago #1932 by Delphine Rea

Replied by Delphine Rea on topic A 19 yo on asciminib as 4L

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

Last edit: 1 year 1 month ago by arlene.

Tim Hughes
Topic Author

1 year 1 month ago - 1 year 1 month ago #1933 by Tim Hughes

Replied by Tim Hughes on topic A 19 yo on asciminib as 4L

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

Last edit: 1 year 1 month ago by arlene.

Nobuko Hijiya
Topic Author

7 months 5 days ago - 7 months 5 days ago #1951 by Nobuko Hijiya

Replied by Nobuko Hijiya on topic A 19 yo on asciminib as 4L, new updates

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

Last edit: 7 months 5 days ago by arlene.

Jeffrey Lipton
Topic Author

7 months 4 days ago #1952 by Jeffrey Lipton

Replied by Jeffrey Lipton on topic A 19 yo on asciminib as 4L

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

Michael Mauro
Topic Author

7 months 3 days ago #1953 by Michael Mauro

Replied by Michael Mauro on topic A 19 yo on asciminib as 4L

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

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