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Table 4 Baseline characteristics and disposition at end-of-study3

From: Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee

  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)
  1. CML chronic myeloid leukemia, CP chronic phase, MMR major molecular response, ND not determined, TKI tyrosine kinase inhibitor
  2. 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%)
  3. bAssessed by conventional Sanger sequencing at baseline
  4. 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
  5. 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
  6. 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)
  7. fPatients who continued to derive clinical benefit from their treatment had the option to receive ponatinib through alternative mechanisms
  8. 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