One of my 51 years old female patient with CML-CP was started on nilotinib 300 mg PO BID on ENSTXTND trial in July 2012. She developed F359V mutation (VAF 100% clone size) in four months of starting nilotinib. Hence, switched over to dasatinib 100 mg PO daily. within six months of starting dasatinib she developed T315I mutation while F359V mutations was not detected. In view of T315I mutation she was switched over to ponatinib. Pleasingly she achieved sustained deep molecular remission within six months of starting ponatinib. Deep molecular response is maintained for last 9 years. She is tolerating ponatinib 30 mg PO daily well, apart from hypertension which is controlled and macular erythematous skin rash which is stable for last eight to nine years and it does not bother her as much.

Would you consider trial of cessation of ponatinib?

Hi Devendra

That is a great question.

Options:

Continue ponatinib long-term – accept the cumulative risk of vascular events which is significant on ponatinib 30 mg/day.

Reduce dose to 15 mg/day – she may lose response but that can probably be overcome quickly with a dose increase.

Switch to asciminib – less vascular risk, good chance of maintaining a deep response. Not currently possible unless she is ponatinib intolerant.

Stop and attempt TFR – this is possible and justifiable if there are major toxicities or side effects but we don’t have any reassuring data in this setting. The risk of BC may be quite high given her propensity to develop mutations.

I would probably recommend a dose reduction of ponatinib to 15 mg/day which we know has a relatively low risk of vascular events, but if she is determined to try TFR, fine as long as she knows the risks are significant. When asciminib becomes available this would be worth considering.

Tim


ORIGINAL CASE – Dr Devendra Hiwase

One of my 51 years old female patient with CML-CP was started on Nilotinib 300 mg PO BID on ENSTXTND trial in July 2012. She developed F359V mutation (VAF 100% clone size) in four months of starting nilotinib. Hence, switched over to dasatinib 100 mg PO daily. within six months of starting dasatinib she developed T315I mutation while F359V mutations was not detected. In view of T315I mutation she was switched over to Ponatinib. Pleasingly she achieved sustained deep molecular remission within six months of starting ponatinib. Deep molecular response is maintained for last 9 years. She is tolerating ponatinib 30 mg PO daily well, apart from hypertension which is controlled and macular erythematous skin rash which is stable for last eight to nine years and it does not bother her as much.

Would you consider trial of cessation of ponatinib?