Case and treating physician are located in Armenia.

63 yo lady who was diagnosed CML CP in March of 2002. Started treatment with busulfan until the 1st gen TKI availability. Treatment continued with Imatinib 400mg daily since Jan 2003.

When the RT-PCR was available, the 1st monitoring was done in February of 2021 by Cepheid GenXpert: 46.83%. Treatment switched to 2nd gen TKI nilotinib 400mg BID, but dose was reduced to 400mg daily because of hematotoxicity and sometimes interrupted. In August of 2022 RT-PCR p210 was 23.93%. We decided to switch treatment to 3rd gen TKI Ponatinib 45mg daily, but unfortunately patient had some complications and we had to reduce dose to 15mg daily and sometimes interrupted treatment. She had unexplained fever 39C and more. So, we decided to stop the treatment and started Bosutinib 400mg daily since July 2024. She tolerated well, but we didn't observe improvement in CBC. She continued to have anaemia and was transfusion dependent. So after 3-4 months of treatment we stopped bosutinib. Now 23.05.2025 CBC: Hb 85g/L, WBC-4.68, Neut.-1.74, PLT-194.0, bone marrow - 3% blast cells, PCR p210 -30.72%.

The problem is that only available (by The Max Foundation) TKI's in Armenia: imatinib, nilotinib and ponatinib. There's no other treatment available in Armenia. What will be your advice for this patient? Return back to Imatinib which was well tolerated and showed stability or prescribe Asciminib?

Very challenging case.

The physician should be commended for managing the patient for the last 20+ years without optimal resources.

If I understand correctly - the patient has never been documented to have achieved MMR.

I note the patient is still of an age where allogeneic stem cell transplant may be considered, but will assume that access is difficult.

Mutation analysis would help, but again, may not be available.

I would also be interested in whether there are additional cytogenetic abnormalities or morphological features suggestive of concurrent MDS, which may contribute to the cytopenia.

In the context of MDS, if the patient has renal dysfunction or inappropriately low epo, supplementation may help. Solving this problem may allow you to increase the intensity of TKI treatment.

If there is no other mitigating factor, and only CML is involved...
The only other licensed agent is asciminib – it would probably have a 30% chance of working in a patient with prior ponatinib exposure. I understand that access is difficult.
In its absence, if it is possible to try ponatinib again, I think that would still offer the best chance of response. But if this is not clinically appropriate due to prior toxicity, choosing imatinib is understandable if this is the best tolerated (consideration may be given to increase the dose to 600mgQD).

Thanks for sharing this case

This is tricky as I’m not sure what the toxicities were with ponatinib? Did she obtain a response to ponatinib?
Does the marrow show fibrosis and does the patient have splenomegaly?
Is it possible to obtain erythropoietin in Armenia? If so, I would try re-starting bosutinib (I can see this isn’t one of the Max Foundation TKIs so not sure how this was obtained) at 300mg with Epo support.
Not sure if asciminib is available, but that could be an option. If it is, I would start at a low dose (20-40mg od), again with Epo support if available.