Table 4.
Baseline characteristics and disposition at end-of-study3
| CP-CML n = 270 |
Total N = 449 |
|
|---|---|---|
| Characteristic at baseline | ||
| Median age (range), y | 60 (18–94) | 59 (18–94) |
| Female, n (%) | 126 (47) | 211 (47) |
| Previous use of approved TKIs, n (%)a | ||
| ≥ 2 drugs | 251 (93) | 417 (93) |
| ≥ 3 drugs | 154 (57) | 250 (56) |
| Median duration of previous treatment with approved TKIs (range), ya | 5.4 (0.4–13.3) | 4.6 (0.1–13.3) |
| Resistant or intolerant to dasatinib or nilotinib, n (%) | ||
| Resistant | 215 (80) | 375 (84) |
| Intolerant only | 39 (14) | 49 (11) |
| Both resistant and intolerant | 52 (19) | 81 (18) |
| Mutation status, n (%)b | ||
| No mutation detected | 138 (51) | 198 (44) |
| BCR::ABL1T315I | 64 (24) | 128 (29) |
| Best response of MMR or better to most recent regimen containing dasatinib or nilotinib, n (%)c | 8 (3) | 16 (4) |
| Baseline cardiovascular risk factorsd | ||
| Arterial hypertension | NA | 240 (53) |
| Hypercholesterolemia | NA | 219 (49) |
| Obesity | NA | 109 (24) |
| Diabetes mellitus | NA | 72 (16) |
| Baseline history of cardiovascular disease | ||
| Non-ischemic cardiac disease | NA | 193 (43) |
| Ischemic disease | NA | 102 (23) |
| Patient disposition at end of study | ||
| Median duration of treatment, mo (range) | 32.1 (0.1–73.0) | 16.7 (0.03–73.0) |
| Median follow-up, mo (range) | 56.8 (0.1–73.1) | 37.3 (0.1–73.1) |
| Median dose intensity, mg/d (range) | 27.2 (5–45) | ND |
| Primary reason for discontinuation, n (%) | ||
| Disease progression | 29 (11) | 105 (23) |
| Adverse event | 57 (21) | 79 (18) |
| Patient request | 31 (11) | 42 (9) |
| Lack of efficacy | 15 (6) | 26 (6) |
| Deathe | 9 (3) | 26 (6) |
| Investigator decision | 11 (4) | 17 (4) |
| Lost to follow-up | 0 | 3 (< 1) |
| Non-compliance | 3 (1) | 4 (< 1) |
| Protocol violation | 2 (< 1) | 2 (< 1) |
| Study closuref | 90 (33) | 107 (24) |
| Otherf,g | 14 (5) | 28 (6) |
CML chronic myeloid leukemia, CP chronic phase, MMR major molecular response, ND not determined, TKI tyrosine kinase inhibitor
aApproved TKIs were imatinib, nilotinib, dasatinib, and bosutinib. Previous investigational TKIs received by at least 1% of patients included radotinib (received by 2% of patients), bafetinib (2%), rebastinib (2%), and XL-228 (2%)
bAssessed by conventional Sanger sequencing at baseline
cPercentages were calculated according to the number of patients who received previous dasatinib or nilotinib: 256 patients with CP-CML, 80 patients with AP-CML, 61 patients with BP-CML, and 30 patients with Ph+ ALL
dSmoking and family history were not collected as part of the trial. Patients with significant or active cardiovascular disease, including myocardial infarction, unstable angina or congestive heart failure (in prior 3 months), or history of clinically significant atrial or ventricular arrhythmia were excluded from the trial
eSeven deaths were assessed by investigators as possibly or probably related to ponatinib (CP-CML: pneumonia, acute myocardial infarction; AP-CML: fungal pneumonia, gastrointestinal hemorrhage; BP-CML: hemorrhagic gastritis; Ph+ ALL: cardiac arrest, mesenteric arterial occlusion)
fPatients who continued to derive clinical benefit from their treatment had the option to receive ponatinib through alternative mechanisms
gThis category includes stem cell transplantation (in 11 patients with CP-CML, 5 with AP-CML, 6 with BP-CML, and 1 with Ph+ ALL). The 9 CP-CML patients and 1 AP-CML patient who remained on study at the time of last response assessment are not included in this category.3