Clinical Case Discussion Forum

To share and enhance best practice management of CML, experts and interested clinicians can discuss difficult or interesting CML cases here. Physicians submit a brief history of the patient and the case for discussion using this forum.

K245N mutation

Topic K245N mutation was created by Dr Susanne Saussele
Dr Susanne Saussele Germany 02:10 12 October 2022

Male patient, 50 years old at diagnosis, CML since 11/2019, initial CP, Ph pos, typical transcript, no comorbidities.

Started with nilotinib treatment 11/2019, BCR >1% after 1 Year (3.5%), Dasatinib not tolerated, switch to ponatinib 30mg 1/21 (within a study) increased to 45 mg 6/21 (BCR-ABL 0.5%)

As the BCR::ABL1 level increased in March this year (0.6%) a mutational analysis was performed in 2 labs . One lab detected the K245N mutation.

Since then BCR:ABL1 decreased to 0.2% but is stable for 3 months now, still no MMR.

We recommended an allo SCT as the mutation appeared. But only one donor with mismatch was detected. One son (17 years old) could be a haplo donor.

Patient’s wish is to try asciminib.

What would you do?

Reply by Dr Delphine Rea on topic K245N mutation
Dr Delphine Rea France 02:18 12 October 2022

This mutation is not well know.

Whether asciminib would be efficient is uncertain due to lack of data.

Vodobatinib in trial may also be attempted but again, no set of data against this mutation.

I would not transplant.

I would try to know what is the size of the mutated clone by ngs. I may maintain pona provided stability of mrd ... and change upon increase. Difficult indeed.

Best regards,

Delphine

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