I think there is a very narrow window here and if the response to ponatiib is lost than the chance of any long-term control is gone. If a donor is available, I would continue ponatinib right until patient is admitted for transplant and restart after a rapid discontinuation of immunosuppression by day 60. If there is no transplant option, then unfortunately it does not really matter and ponatinib could be held until count revovery.

Very unfortunate case.

Within the MATCHPOINT clinical trial, we started ponatinib 30mg on day 1 of induction chemotherapy (FLAG-IDA). We continued the ponatinib until day 28 of each cycle. If there was no count recovery by day 28, then the ponatinib was stopped, and then re-started once counts had recovered (grade 2 or better). The ponatinib (at a dose of 30mg if not in CCyR) or 15mg if in CCyR was then continued until admission from conditioning for alloSCT. Where possible, ponatinib 15mg was re-started post SCT.

In this case, I would stop the ponatinib if grade 3 cytopenias are continuing, until resolved to grade 2 or better (Plt>50x10^9/L and Neut >1x10^9/L. For this patient, given their age, if they are fit enough and have a suitable donor, then I would proceed to alloSCT, even if only minimal cytogenetic response to the second DA3+7 with ponatinib. If there is no transplant option or this is delayed, and the patient isn’t in CCyR, then I would repeat a mutation screen and aim to give the patient ponatinib 45mg.

I am happy to discuss further.

I’m consultant clinical Hematologist and BMT physician in a LMIC.

I have a query regarding TKI in blast crisis.

I have a 23yrs old female, case of CML for last three years, TKI resistant, F359V mutation positive, now transformed into Blast crisis. She received First cycle of Induction D3A7 with Ponatinib 15mgOD (dose reduced secondary to Drug rash?). Post first cycle she is not in morphological remission. She was given second D3A7 with 45mg OD of Ponatinib, which she tolerated well. Now awaiting count recovery.

My question is about TKI, when should it be started during induction? On day 1 or afterwards? And should we stop Ponatinib for grade 3 cytopenias post Induction, which are likely due to disease? Shouldn’t we hit the disease with this targeting agent? Or to make it simple do we need TKI in this case to achieve remission or will the two cycles of inductions be sufficient?

Regards,
Dr Saima Humayun Toor