1. Opinion regarding further reduction in ponatinib dose? I would continue 30 mg at the minimum to the 36 months and possibly longer if the patient has no problems. He is young and if he has no risk features for arterio-occlusive events the risk is low, certainly lower compared to the risk of death if he recurs.

2. Would anyone consider discontinuing ponatinib at any time? A patient who has been in blast phase is not a candidate for TFR so I would not consider stopping ponatinib at any point.

CML case
18 year old male presented in March, 2010 with CML chronic phase but with 9 additional chromosome abnormalities.
Started on imatinib and initially responded well, but had issues with tolerance and switched to dasatinib in 2012 when it became evident that intolerance was leading to poor compliance.
Initially tolerated dasatinib well, but again had significant compliance issues and presented in 2015 with acceleration. Cytogeneitics showed 10 additional chromosomal abnormalities.
Dasatinib dose was increased and unrelated donor search initiated.
Underwent 9/10 A-mismatched MUD transplant now in CP2 after conditioning with Flu4Bu4TBI400 in July 2015.
Grade 1, stage 1 acute GVHD skin treated with topical steroid.
Immunosuppression discontinued by day 100.
Molecular relapse with loss of MMR by day 120 and dasatinib restarted with stabilization of molecular response at roughly 3-log.
At 6 months developed ITP and prednisone/IVIG initiated with transient response. Treated with 4 course of rituximab with good response. Dasatinib continues.
At 7 months right thoracic shingles.
By 9 months molecular response now >4-log.
By 12 months molecular response down to 3-log. Dasatinib dose increased to 140mg daily.
At 15 months, blast crisis – myeloid with 25% blasts.
Started on ponatnib 45mg daily and within 2 months was in CP3 with MMR and was scheduled for second MUD allograft from different A-mismatched donor.
On admission for allograft in September 2015, again found to be in blast crisis. Transferred to acute leukemia service and underwent induction with FLAG-Ida. Achieved CP4!
Underwent second stem cell allograft from different A-mismatched MUD from first transplant after RITC conditioning with Flu4Bu2TBI200 conditioning.
Acute GVHD skin, stage 2, grade 1 treated with topic steroid.
Immunosuppression discontinued by day 80.
Recurrent thoracic shingles at day 70 treated with famcyclovir.
Ponatinib 45 mg resumed at day 85 after discontinuation of famcyclovir.
Undetectable bcr-abl (5-log sensitive assay IS) by day 60. Continues now 30 months post allograft.
Ponatinib reduced to 30 mg daily after 18 months. Plan to reduce to 15 mg daily after 36 months.
QUESTION
1. Opinion regarding further reduction in ponatinib dose
2. Would anyone consider discontinuing ponatinib at any time