Safety Profile of ICLUSIG (ponatinib) in the PACE trial

PACE established the safety profile for ICLUSIG in patients with Ph+ ALL1

Adverse Reactions (≥20%) in Patients with Ph+ ALL

Adverse reactions in patients with Ph+ALL who received ICLUSIG include: Rash and related conditions, dry skin, arthralgia, abdominal pain, cons pa on, nausea, vomiting, fatigue or asthenia, fluid retention and edema, pyrexia, headache, hypertension, hemorrhage, cardiac arrhythmias, pneumonia, sepsis, decreased appetite, febrile neutropenia.

aDerived from BP measurement.
bSepsis includes abdominal sepsis, bacteremia, device-related sepsis, escherichia bacteremia, fungemia, klebsiella bacteremia, klebsiella sepsis, neutropenic sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal bacteremia, and urosepsis. Graded using Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

Serious Adverse Reactions2

Serious adverse reactions occurred in 69% of patients who received ICLUSIG. Serious adverse reactions in >2% of patients included AOEs (20%), pneumonia (10%), cardiac arrhythmias (8%), pancreatitis/lipase elevation (7%), abdominal pain (6%), cardiac failure (6%), hemorrhage (6%), sepsis (5%), VTEs (5%), fluid retention and edema (4.5%), pyrexia (4.5%), secondary malignancies (5%), anemia (3.3%), hypertension (3.1%), thrombocytopenia (3.1%), febrile neutropenia (2.9%), cellulitis (2.7%), and arthralgia (2.2%). Fatal adverse reactions occurred in 9% of patients who received ICLUSIG; the most frequent fatal adverse reactions were AOEs (2%), sepsis (1.6%), and hemorrhage (1.3%). 

Arterial Occlusive Events2

26% of 449 patients experienced AOEs, of which 15%, 7%, and 11% experienced cardiovascular, cerebrovascular, and peripheral vascular AOEs, respectively. Some patients experienced recurrent or multisite vascular occlusion.

  • Grade 3 or 4 AOEs occurred in 14% of patients; the most frequent Grade 3 or 4 AOEs were peripheral arterial occlusive disease (3.1%), myocardial infarction (2%), coronary artery disease (1.6%), and cerebral infarction (1.6%). Fatal AOEs occurred in 9 patients (2%); the most frequent fatal AOE was cardiac arrest (0.9%). 

Discontinuation Rates2

Permanent discontinuation of ICLUSIG due to an adverse reaction occurred in 21% of CP‑CML, 12% of AP-CML, 15% of BP-CML, and 9% of Ph+ ALL patients. The most frequent adverse reactions that led to treatment discontinuation were thrombocytopenia (4.5%) and AOEs (4%).

Please see the full Prescribing Information for a full list of adverse reactions.

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AOE=arterial occlusive effect; AP-CML=accelerated-phase chronic myeloid leukemia; BP=blood pressure; BP‑CML=blast phase chronic myeloid leukemia; CP‑CML=chronic phase chronic myeloid leukemia; Ph+ ALL=Philadelphia chromosome-positive acute lymphoblastic leukemia; VTE=venous thromboembolic event; WBC=white blood cell.