ICLUSIG® (ponatinib) Adverse Reactions from the PACE trial.

Discontinuation rates in the PACE trial due to treatment-emergent adverse reactions:

  • 19% of CP-CML patients
  • 12% of AP-CML patients
  • 15% of BP-CML patients
  • 9% of Ph+ ALL patients

Myelosuppression was commonly reported in all patient populations. The frequency of grade 3 or 4 thrombocytopenia, neutropenia, and anemia was higher in patients with AP-CML, BP-CML, and Ph+ ALL than in patients with CP-CML.

Adverse reactions in > 10% of patients in the PACE trial (N=449)
CP-CML (N=270) AP-CML (N=85) BP-CML (N=62) Ph+ ALL (N=32)
Body System Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)
Cardiac or vascular disorders
Hypertensiona 69 42 74 42 60 23 53 28
Arterial ischemiab 42 17 28 14 11 8 22 6
Cardiac failurec 8 5 7 5 15 8 6 3
Gastrointestinal disorders
Abdominal paind 48 10 42 9 35 8 34 6
Constipation 41 3 27 2 27 0 53 3
Nausea 28 1 31 0 34 2 22 0
Diarrhea 20 1 29 2 24 3 13 3
Vomiting 18 2 26 0 27 2 25 0
Oral mucositise 14 1 19 1 23 0 9 3
Gl hemorrhagef 1 <1 8 1 6 3 9 6
Adverse reactions in > 10% of patients in the PACE trial (N=449)
CP-CML (N=270) AP-CML (N=85) BP-CML (N=62) Ph+ ALL (N=32)
Body System Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)
Blood and lymphatic system disorders
Febrile neutropenia 1 1 5 5 13 13 25 25
Infections and Infestations        
Sepsis 2 1 4 4 3 0 13 13
Pneumonia 6 5 13 9 16 11 9 3
Urinary tract infection 11 2 14 2 2 2 9 0
Upper respiratory tract infection 14 1 13 0 13 2 3 0
Nasopharyngitis 12 0 18 0 3 0 3 0
Cellulitis 3 2 6 2 11 3 0 0
Adverse reactions in > 10% of patients in the PACE trial (N=449)
CP-CML (N=270) AP-CML (N=85) BP-CML (N=62) Ph+ ALL (N=32)
Body System Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)
Nervous system disorders
Headache 43 3 29 0 31 3 25 0
Peripheral neuropathy 24 3 14 1 11 0 16 0
Dizziness 16 0 9 0 5 0 3 0
Respiratory, thoracic, and mediastinal disorders
Pleural effusion 5 2 12 2 13 0 19 3
Cough 16 0 22 0 19 0 6 0
Dyspnea 17 3 20 4 19 5 6 0
Adverse reactions in > 10% of patients in the PACE trial (N=449)
CP-CML (N=270) AP-CML (N=85) BP-CML (N=62) Ph+ ALL (N=32)
Body System Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)
Skin and subcutaneous tissue disorders
Rash and related conditions 63 4 59 7 39 5 28 3
Dry skin 42 3 32 1 26 2 25 0
Pruritis 13 <1 8 0 5 2 0 0
Erythema 10 1 8 0 8 0 6 0
Alopecia 7 0 11 0 8 0 6 0
Musculoskeletal and connective tissue disorders
Arthralgia 32 3 33 2 19 0 13 0
Myalgia 24 1 20 0 18 0 6 0
Pain in extremity 23 3 19 0 13 0 13 0
Back pain 21 1 14 2 19 2 13 0
Muscle spasms 14 0 6 0 5 0 13 0
Bone pain 14 <1 13 1 11 3 9 3
Musculoskeletal pain 11 2 7 0 8 0 6 3
Adverse reactions in > 10% of patients in the PACE trial (N=449)
CP-CML (N=270) AP-CML (N=85) BP-CML (N=62) Ph+ ALL (N=32)
Body System Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)
General disorders and administration site conditions
Fatigue or asthenia 47 4 49 8 40 6 34 3
Pyrexia 26 1 40 7 36 3 25 0
Edema, peripheral 16 <1 18 0 15 0 25 0
Pain 10 <1 13 0 16 3 6 0
Chills 8 0 11 0 13 2 9 0
Metabolism and nutrition disorders
Decreased appetite 13 <1 14 1 8 0 31 0
Adverse reactions in > 10% of patients in the PACE trial (N=449)
CP-CML (N=270) AP-CML (N=85) BP-CML (N=62) Ph+ ALL (N=32)
Body System Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)		 Any grade
(%)		 Grade 3/4
(%)
Investigations
Weight decreased 10 <1 9 0 5 0 13 0
Psychiatric disorders
Insomnia 11 0 13 0 11 0 13 0

Adverse drug reactions, reported using MedDRA and graded using NCI-CTC-AE v 4.0 (NCI Common Terminology Criteria for Adverse Events) for assessment of toxicity.
Treatment-emergent, all causality events.

a Derived from blood pressure (BP) measurement recorded monthly while on trial
b Includes cardiovascular, cerebrovascular, and peripheral vascular ischemia
c Includes cardiac failure, cardiac failure congestive, cardiogenic shock, cardiopulmonary failure, ejection fraction decreased, pulmonary edema, right ventricular failure
d Includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort
e Includes aphthous stomatitis, lip blister, mouth ulceration, oral mucosal eruption, oral pain, oropharyngeal pain, pharyngeal ulceration, stomatitis, tongue ulceration
f Includes gastric hemorrhage, gastric ulcer hemorrhage, hemorrhagic gastritis, gastrointestinal hemorrhage, hematemesis, hematochezia, hemorrhoidal hemorrhage, intra-abdominal hemorrhage, melena, rectal hemorrhage, and upper gastrointestinal hemorrhage
g Includes burning sensation, skin burning sensation, hyperesthesia, hypoesthesia, neuralgia, neuropathy peripheral, paresthesia, peripheral sensorimotor neuropathy, peripheral motor neuropathy, peripheral sensory neuropathy, polyneuropathy, dysgeuisa, muscular weakness, gait disturbance, nerve compression, areflexia, hypotonia, restless legs syndrome