Safety Profile of ICLUSIG (ponatinib) in the PACE trial
PACE established the safety profile for ICLUSIG in patients with CML1
Adverse Reactions (>10%) in Patients with CML Who Received ICLUSIG in PACE2
CP-CML (N=270)2
Graded using CTCAE.2
aOral mucositis includes aphthous ulcer, gingival pain, lip blister, lip pain, lip swelling, mouth ulceration, oropharyngeal pain, oral mucosal blistering, oral mucosal eruption, oral pain, pharyngeal ulceration, stomatitis, and tongue ulceration.2
bDerived from blood pressure (BP) measurement.2
cCough includes cough, productive cough, and upper airway cough syndrome.2
dDyspnea includes dyspnea and dyspnea exertional.2
eUpper respiratory tract infection includes upper respiratory tract infection and viral upper respiratory tract infection.2
fUrinary tract infection includes escherichia urinary tract infection, urinary tract infection, and urinary tract infection bacterial.2
gSepsis 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.2
AP-CML (N=85)2
Graded using CTCAE.2
aOral mucositis includes aphthous ulcer, gingival pain, lip blister, lip pain, lip swelling, mouth ulceration, oropharyngeal pain, oral mucosal blistering, oral mucosal eruption, oral pain, pharyngeal ulceration, stomatitis, and tongue ulceration.2
bDerived from blood pressure (BP) measurement.2
cCough includes cough, productive cough, and upper airway cough syndrome.2
dDyspnea includes dyspnea and dyspnea exertional.2
eUpper respiratory tract infection includes upper respiratory tract infection and viral upper respiratory tract infection.2
fUrinary tract infection includes escherichia urinary tract infection, urinary tract infection, and urinary tract infection bacterial.2
gSepsis 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.2
BP-CML (N=62)2
Graded using CTCAE.2
aOral mucositis includes aphthous ulcer, gingival pain, lip blister, lip pain, lip swelling, mouth ulceration, oropharyngeal pain, oral mucosal blistering, oral mucosal eruption, oral pain, pharyngeal ulceration, stomatitis, and tongue ulceration.2
bDerived from blood pressure (BP) measurement.2
cCough includes cough, productive cough, and upper airway cough syndrome.2
dDyspnea includes dyspnea and dyspnea exertional.2
eUpper respiratory tract infection includes upper respiratory tract infection and viral upper respiratory tract infection.2
fUrinary tract infection includes escherichia urinary tract infection, urinary tract infection, and urinary tract infection bacterial.2
gSepsis 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.2
Serious Adverse Reactions2
Serious adverse reactions occurred in 69% of patients who received ICLUSIG (N=449 [417 CML patients and 32 Ph+ ALL patients]). 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 patients experienced AOEs, of which 15%, 7%, and 11% experienced cardiovascular, cerebrovascular, and peripheral vascular AOEs, respectively.
- 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%).
- In PACE, fatal and life-threatening AOEs occurred within 2 weeks of starting treatment at 45 mg, and at dose levels as low as 15 mg per day. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced AOEs.
- AOEs were more frequent with increasing age and in patients with history of ischemia, hypertension, diabetes, or hypercholesterolemia. The most common risk factors in patients with AOEs were history of hypertension (67%; 77/115), hypercholesterolemia (59%; 68/115), and nonischemic cardiac disease (43%; 49/115).
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 and arterial occlusive events.
Explore the efficacy of ICLUSIG in Ph+ ALL
Review the safety profile of ICLUSIG in OPTIC
AOE=arterial occlusive event; AP‑CML=accelerated-phase chronic myeloid leukemia; BP‑CML=blast-phase chronic myeloid leukemia; CML=chronic myeloid leukemia; CP‑CML=chronic-phase chronic myeloid leukemia; Ph+ ALL=Philadelphia chromosome-positive acute lymphoblastic leukemia; VTE=venous thromboembolic event.