AOEs
AOE baseline and monitoring recommendations for patients on ICLUSIG
If a patient is resistant to a therapy, additional workup should be conducted prior to initiating a new therapy. Treatment considerations independent of risk score include comorbidities and patient preference. When initiating ICLUSIG, HCPs should consider the benefit-risk profile of each therapy.
-There are no testing recommendations specific to AOEs before patients start ICLUSIG. The Medication Guide recommends that patients tell their HCP if they have a history of blood clots. HCPs should monitor for evidence of AOEs while a patient is taking ICLUSIG.
-HCPs should be aware of dose modifications that can be made to manage AOEs including serious ones from Boxed Warning.
VTE: Baseline and monitoring recommendations for patients on ICLUSIG?
If a patient is resistant to a therapy, additional workup should be conducted prior to initiating a new therapy. Treatment considerations independent of risk score include comorbidities and patient preference. When initiating ICLUSIG, HCPs should consider the benefit-risk profile of each therapy.
The PI does not provide any specific recommendations for testing before starting ICLUSIG as related to VTEs. It recommends ongoing monitoring for evidence of VTEs. The HCP should consider interrupting or discontinuing ICLUSIG based on the recurrence and severity of the AR.
HCPs should be aware of dose modifications that can be made to manage VTEs including serious ones. Preference should be to interrupt, then resume at the same dose or decreased dose or discontinue ICLUSIG based on recurrence/severity.
Can I use ICLUSIG in patients that currently have liver disease?
There is no specific contraindication, and each HCP and patient must decide based on a benefit-risk decision that takes into account the individual patient's situation. Patients with hepatic impairment require a reduced starting dose of ICLUSIG, as they are more likely to experience adverse reactions with the recommended starting dose of 45 mg compared to patients with normal hepatic function. Section 2.4 recommends starting at 30 mg orally once daily in patients with pre-existing hepatic impairment (Child-Pugh A, B, or C).
How frequently was heart failure seen in the OPTIC and PACE studies?
-In OPTIC, any grade of heart failure occurred in 12% of patients, 1.1% was Grade 3 or 4.
Fatal or serious heart failure events occurred in PACE. Any grade of heart failure (in 449 patients) was 9%, grade 3 or higher occurred in 7% of patients.
Favorite training class
ICLUSIG duh!
AOEs rates in OPTIC
OPTIC had an overall AOE rate of 13%. The rate of Grade 3 or 4 AOEs was 5%.
When considering all grades, the type of occlusive event was cardiovascular in 9%, cerebrovascular in 2.1% and peripheral vascular in 2.1%.
- The most frequent Grade 3 or 4 AOEs included myocardial infarction, acute coronary syndrome, arterial thrombosis, ischemic stroke, and ischemic cerebral infarction in 1.1% each. 2 patients experienced fatal AOEs, both of which were sudden death.
Can I use aspirin to prevent clots?
This is not addressed in the PI and requires a MIRF.
Are there any specific monitoring recommendations for patients if hepatotoxicity occurs while on ICLUSIG?
Monitor liver function tests at baseline, then at least monthly or as clinically indicated.
HCPs should be aware of dose modifications that can be made to manage hepatotoxicity including serious ones from Boxed Warning. Interrupt, then resume at reduced dose or discontinue ICLUSIG based on recurrence/severity.
What are the baseline and monitoring recommendations for patients on ICLUSIG?
If a patient is resistant to a therapy, additional workup should be conducted prior to initiating a new therapy. Treatment considerations independent of risk score include comorbidities and patient preference. Prior to initiating ICLUSIG, HCPs should consider the benefit-risk profile of each therapy.
There are no baseline tests that are routinely recommended for HCPs related to heart failure in the ICLUSIG PI.
Monitor patients for signs or symptoms consistent with heart failure and manage heart failure as clinically indicated. Interrupt, then resume at reduced dose or discontinue ICLUSIG for new or worsening heart failure.
HCPs should be aware of dose modifications that can be made to manage heart failure.
What year was ICLUSIG FDA approved?
2012
Median time to onset in OPTIC and PACE
OPTIC: The median time to onset of the first cardiovascular event was 4.5 months (range 12 days-2.1 years), cerebrovascular event was 1 year (range: 5.9 months to 1.6 years), and peripheral vascular event was 3.6 months (range: 23 days to 6.3 months).
PACE: -The median time to onset of the first cardiovascular AOE was 1 year (range: 1 day to 4.1 years), cerebrovascular AOEs was 1.4 years (range: 2 days to 4.5 years), and peripheral vascular AOEs was 2 years (range: 10 days to 4.9 years).
VTE rates and types seen in OPTIC and PAVE
There was 1 patient in OPTIC who received a starting dose of 45 mg who experienced a retinal vein occlusion.
In PACE, there was an overall rate of VTEs in 6% of 449 patients with Grade 3 or 4 events occurring in 5.8%.
The types of VTEs seen in the entire PACE study population (N=449) included: deep vein thrombosis (DVT) in 2.2%, pulmonary embolism in 1.8%, superficial thrombophlebitis in 0.7%, retinal vein occlusion in 0.7%, and retinal vein thrombosis in 0.4% with vision loss.
Section for Dose Mods for hepatotoxicity
Section 2.2
Exclusion criteria for PACE and OPTIC is located
Section 6.1
What is the date for World CML Day?
AOEs rate in PACE
In PACE, the AOE rate was 26%. The rate of Grade 3 or 4 AOEs was 14%.
-When considering all grades, the type of occlusive event was cardiovascular in 15%, cerebrovascular in 7%, and peripheral vascular in 11%.
-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%).
Median time to onset of venous thromboembolic events
Median time to onset is not mentioned in the PI, and this question would require a MIRF
Section for Dosing guidance for hepatic impairment
Section 2.4
Why were those with cardiovascular (CV) disease excluded in OPTIC
Patients with uncontrolled or active CV disease were excluded from OPTIC due to a known AOE and cardiovascular risk seen with ICLUSIG.
OPTIC excluded patients with clinically significant uncontrolled or active CV disease. These are outlined in Section 6.1 of the PI.
Describe the MOA
The only 3rd gen TKI for the treatment of CML that is purposefully engineered to inhibit BCR-ABL1 regardless of mutation status
What patient is not a candidate for ICLUSIG due to risk for arterial occlusive events?
-There is no contraindication to using ICLUSIG due to prior arterial occlusive events, however, the physician must make a benefit-risk decision along with the patient. Section 5.1 recommends that the HCP considers whether the benefits of ICLUSIG are expected to exceed the risks.
-When considering a patient’s risk for an AOE on ICLUSIG, it is important to remember that patients with and without cardiovascular risk factors, including patients less than 50 years or younger may experience AOEs. AOEs were more frequent with increasing age and in patients with history of ischemia, hypertension, diabetes, or hypercholesterolemia. The most common risk factors from PACE in patients with AOEs were hypertension, hypercholesterolemia, and non-ischemic cardiac disease.
-In OPTIC, patients with uncontrolled hypertension or diabetes and patients with clinically significant, uncontrolled, or active cardiovascular disease, including any history of myocardial infarction, peripheral vascular infarction, revascularization procedure, congestive heart failure, venous thromboembolism, or clinically significant atrial/ventricular arrhythmias, were excluded. In PACE, patients with uncontrolled hypertriglyceridemia and patients with clinically significant or active cardiovascular disease, including any history of clinically significant atrial/ventricular arrhythmias or history of myocardial infarction, unstable angina, or congestive heart failure within the 3 months prior to the first dose of ICLUSIG, were excluded.
When is my patient not a candidate for ICLUSIG due to a risk of VTE?
There is no contraindication to using ICLUSIG due to prior venous thromboembolic events, however, the physician must make a benefit risk decision along with the patient. Section 5.2 recommends that the HCP considers whether the benefits of ICLUSIG are expected to exceed the risks.
The Medication Guide recommends patients tell providers if they have a history of blood clots.
Rates of hepatotoxicity and median time to onset for patients in the OPTIC and PACE trials
OPTIC: all grades 25%, Grade 3 or 4 was 6%. The median time to onset of hepatotoxicity was 1.9 months, with a range of 3 days to 1.9 years.
PACE: all grades 32% (of 449 patients), Grades 3 or 4 was 13%. The median time to onset of hepatoxicity was 3.1 months, with a range of 1 day to 4.9 years.
It is important to note that the PI reports ICLUSIG can cause liver failure and death. Fulminant hepatic failure leading to death occurred in 3 patients, with hepatic failure occurring within 1 week of starting Iclusig in one of these patients. These fatal cases occurred in patients with BP-CML or Ph+ ALL.
When is my patient not a candidate for ICLUSIG due to risk for heart failure?
There is no contraindication to using ICLUSIG due to prior heart failure, however, the physician must make a benefit risk decision along with the patient. Section 5.3 recommends the physician must make a benefit risk decision along with the patient based on the fact that patients with a history of heart failure were excluded from OPTIC and non-ischemic cardiac disease was associated with increased risk of AOEs in PACE.
What is #priority1
There are hundreds of appropriate patients in the United States who could potentially benefit from the opportunity to receive ICLUSIG. Our #1 priority is to do our best to provide these patients with that opportunity.