Table 1.
Low-dose ponatinib efficacy and safety outcomes from real-life observations.
| Study | Patient population | Ponatinib starting dose per day | Median duration of treatment | Efficacy and safety outcomes |
|---|---|---|---|---|
| Mauro et al. (16) | CML pts | Low-dose ≤30 mg (15 pts) Standard dose >30 mg (20 pts) |
11 mo (≤30 mg/d) 12 mo (>30 mg/d) |
• Efficacy response similar with low- and standard-dose ponatinib (40% low-dose pts vs. 25% standard-dose pts achieved MMR or better; p = 0.344) • No significant between-group differences in AESI, including AOEs |
| Binotto et al. (17) | CP-CML pts resistant or intolerant to previous TKIs | 45 mg (24 pts resistant to prior TKIs) 30 mg (13 pts resistant to prior TKIs) 15 mg (25 pts; 12 pts were intolerant or intolerant/resistant to prior TKIs) |
21.2 mo at any dose 15 mo at 15 mg starting dose |
• 55% of pts treated with 45 mg or 30 mg ponatinib achieved MMR after a median of 4.3 mo • Dose reduction to 15 mg occurred after a median of 10 mo due to AEs (73%) or to prevent toxicity and/or following response attainment (27%) • Efficacy of de-escalated ponatinib dose confirmed in CP-CML pts resistant to prior TKIs • 15 mg as starting dose conferred potential benefit in pts intolerant or with low level resistance (all intolerant and 80% of intolerant/resistant pts achieved MMR or higher) • Hematologic and CV AEs were more frequent in pts receiving ≥30 mg versus 15 mg ponatinib |
| Breccia et al. (18) | CP-CML pts | 45 mg (17 pts) 30 mg (11 pts) 15 mg (1 pts) |
12 mo | • Dose was reduced in 2 pts due to intolerance (from 45 mg to 30 mg) and in 8 pts to reduce CV risk after obtaining a cytogenetic response (from 45 mg to 30 mg and from 30 mg to 15 mg in 4 pts each) • Improved level of response vs baseline in 85.7% of pts at a median of 12 mo (11 pts achieved MMR) • No CV AEs were observed • Ponatinib appears to be efficacious and safe in CML pts who failed front-line treatment with a 2nd-generation TKI |
| Heiblig et al. (19) | CP-CML (48 pts) | Not stated | 19 mo | • OS probability at 12 and 36 mo, respectively, was 95.7% (range 90.04%–100%) and 81.5% (range 70.5%–94%) • The cumulative incidence of MMR was 66.7% and 81.8%, respectively, at 6 and 18 mo • CP-CML pts reported 37 non-severe CV events and 9 severe CV events including thrombotic and non-thrombotic events |
| Iurlo et al. (20) | CP-CML (53 pts) | 45 mg (22 pts) 30 mg (21 pts) 15 mg (9 pts) other dose (1 pt) |
23.9 mo | • Interim analysis of the OITI trial • 88.6% of CP-CML pts achieved a CCyR after 6 mo ponatinib treatment and 37.5% achieved MMR • OS rates were 96.2% and 93.1%, respectively, at 12 and 24 mo • 53.6% (30 pts) had treatment-related AEs; hypertension (n = 6) was the most frequent |
| Iurlo et al. (21) | CML pts intolerant to previous TKIs | 45 mg (9 pts) 30 mg (18 pts) 15 mg (25 pts) |
19.2 mo | • Depth of MR increased in 21 (40.4%) pts including 6 pts with MMR and 15 pts with DMR • AEs were reported in 24 (46.2%) pts; 4 pts experienced CV AEs including one case each of AMI and ischemic stroke both occurring in pts with pre-existing CV risk factors who were initially treated with 30 mg ponatinib |
| Chan et al. (22) | CP-CML (51 pts) | 39.65 mg (mean starting dose) Dose reduction occurred in 64.7% of CP-CML pts |
14.6 mo | • 58.7% of CP-CML pts (27/46) achieved MMR • After 2014, the proportion of pts initiating ponatinib at 45 mg/d decreased substantially (29.3% vs. 86.5% before 2014) • CV events decreased from 2014 onwards following implementation of lower starting doses, early dose reductions, and referral of pts to cardio-oncologists |
| Iurlo et al. (23) | CP-CML pts intolerant to dasatinib | 15 mg (7 pts) | 9.9 mo | • Depth of MR achieved with dasatinib was maintained or increased with low-dose ponatinib; MR increased to MR4 in 2 pts • There were no serious AEs or CV thrombotic issues requiring ponatinib discontinuation; 3 pts developed hypertension |
| Santoro et al. (24) | CML pts with CV risk factors | Median dosage of 30 mg (45–30 mg starting dose reduced to 15 mg) | 34.6 mo | • Stable or improved MR achieved with ponatinib treatment; 4 pts achieved MMR; 1 pt achieved MR4 • Despite a reduction in ponatinib dose to 15 mg, all 5 pts maintained a target MR of at least MMR • No CV AEs were reported |
AEs, adverse events; AESI, adverse events of special interest; AMI, acute myocardial infarction; AOEs, arterial occlusive events; AP, accelerated phase; BP, blast phase; CCyR, complete cytogenetic response; CML, chronic myeloid leukemia; CP, chronic phase; CV, cardiovascular; d, day; DMR, deep molecular response; MR, molecular response; MMR, major molecular response; mo, months; OITI, Observational study of Iclusig® (ponatinib) Treatment in patients with CML in Italy; OS, overall survival; pts, patients; yr, year.