Our patient is a 45-year-old female with CML-CP diagnosed in 03/2020 who was initially treated by imatinib, then dasatinib and progressed to myeloid blast crisis in 07/2020. She was proceeded “7+3+dasatinib” with achievement of second CP. Haploidentical SCT was done on 10/02/2021 with achievement PCR negativity and full donor chimerism. Maintenance treatment with dasatinib was continued after alloHSCT. Molecular progression was detected on +5 months. Dasatinib was replaced by nilotinib, but second blastic phase was diagnosed in a few weeks. The third CP was achieved after “FLA” and maintenance treatment with asciminib 40 mg->80 mg was started.

Due to BCR::ABL transcript level elevation, the dose of asciminib was increased up to 200 mg-> 400 mg with concomitant DLI (five doses totally). Due to further molecular progression, asciminib was replaced by bosutinib, then ponatinib in combination with AZA-VEN. Despite this, the third BP was diagnosed in 04/2024-refractory disease. According to mutational analysis А433Т and del 185bp (c1086-1270, p.362fs*21) were detected (mut analysis was performed several times but no mutations earlier). 

The fourth CP, PCR negativity and full donor chimerism was regained after FLAG+DLI. We have planned the second alloHSCT, matched unrelated donor was activated. AlloHSCT had been delayed due to appearance of acute skin GVHD grade 3, which has resolved after glucocorticosteroid treatment. At present time, her disease is in CP, deep molecular response with detectable BCR-ABLp210 at 0,002% and full donor chimerism. She takes asciminib 80 mg and discontinued immunosupression.

In this situation, would you prefer the second alloHSCT from MUD immediately, or delay it until progression and continue BCR-ABL monitoring with asciminib maintenance?

Considering the case and the deep molecular response achieved, but also all the pre-treatment, I would consider at the moment to continue with asciminib 80 mg with a strict monitoring of MRD, reserving HSCT for a possible further progression.

Difficult but very well managed case.

As a transplanter, I would recommend continuing current management and plan a second AlloBMT with fully HLA matched MUD in case of another blast crisis.

Flow should be done in case of another blast crisis to differentiate AML/ALL/AUL/MPAL.

Dear colleague,

The probability that the response will be maintained with asciminib is extremely low and appears quiet palliative.
So if considered feasible although very risky, a rapid 2nd tranplant might be the best option in the view of a long-term control of the disease.

Best regards,

Dr Delphine Rea

This very unfortunate young woman has had multiple blast crises and has had an allograft with what sounds like some GVH at least acute. She has failed multiple TKIs and chemotherapeutic regimens. Another allograft using a different donor is contemplated at some point. I ask then, what is the goal of therapy? The likelihood of a cure is very remote even with a different donor. It sounds like she is doing well right now with reasonable quality of life. Unfortunately, she will most likely relapse into another blast crisis with or without another allograft which will add to her toxicity. Personally, I would keep her going as long a possible and not even consider another allograft. But, I guess if explained fully, it is her decision. I know she is young, but some of us can just not let go. QOL maximizing palliation is often the best choice. That is what she has now.