IMBRUVICA® IMPROVED SURVIVAL IN PREVIOUSLY TREATED CLL

Phase 3 RESONATE™ trial vs ofatumumab

  • Significantly improved overall survival (OS), with a 57% reduction in risk of death—secondary endpoint
  • Significantly improved progression-free survival (PFS), with a 78% reduction in the risk of progression or death—primary endpoint

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA®. Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA®.

The mechanism for the bleeding events is not well understood.  IMBRUVICA® may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections - Fatal and non-fatal infections have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA®. Monitor patients for fever and infections and evaluate promptly.

Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 9%) occurred in patients treated with IMBRUVICA®. Monitor complete blood counts monthly.

Atrial Fibrillation - Atrial fibrillation and atrial flutter (range, 6 to 9%) have occurred in patients treated with IMBRUVICA®, particularly in patients with cardiac risk factors, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. If atrial fibrillation persists, consider the risks and benefits of IMBRUVICA® treatment and dose modification.

Second Primary Malignancies - Other malignancies (range, 5 to 14%) including non-skin carcinomas (range, 1 to 3%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4 to 11%).

Tumor Lysis Syndrome -  Tumor lysis syndrome has been reported with IMBRUVICA® therapy. Monitor patients closely and take appropriate precautions in patients at risk for tumor lysis syndrome (e.g. high tumor burden).

Embryo-Fetal Toxicity -  Based on findings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA®. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS

The most common adverse reactions (≥25%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia* (57%, 52%, 43%), neutropenia* (47%, 51%, 44%), diarrhea (51%, 48%, 37%), anemia* (41%, 36%, 13%), fatigue (41%, 28%, 21%), musculoskeletal pain (37%, 28%, NA), bruising (30%, 12%, 16%), nausea (31%, 26%, 21%), upper respiratory tract infection (34%, 16%, 19%), and rash (25%, 24%, 22%).

*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

Includes multiple ADR terms.

Not applicable; no associated ADRs.

The most common Grade 3 or 4 non-hematological adverse reactions (≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse events.

Approximately 5% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse events. Most frequent adverse events leading to discontinuation were infections, subdural hematomas, and diarrhea in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors - Avoid co-administration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA® dose.

CYP3A Inducers - Avoid co-administration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment - Avoid use in patients with moderate or severe baseline hepatic impairment.  In patients with mild impairment, reduce IMBRUVICA® dose.

Please review the full Prescribing Information.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088).

Indications

IMBRUVICA® (ibrutinib) is indicated for the treatment of:

  • Patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
  • Patients with chronic lymphocytic leukemia (CLL) with 17p deletion.
  • Patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
    • Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
  • Patients with Waldenström's macroglobulinemia (WM)

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA®. Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA®.

The mechanism for the bleeding events is not well understood.  IMBRUVICA® may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections - Fatal and non-fatal infections have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA®. Monitor patients for fever and infections and evaluate promptly.

Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 9%) occurred in patients treated with IMBRUVICA®. Monitor complete blood counts monthly.

Atrial Fibrillation - Atrial fibrillation and atrial flutter (range, 6 to 9%) have occurred in patients treated with IMBRUVICA®, particularly in patients with cardiac risk factors, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. If atrial fibrillation persists, consider the risks and benefits of IMBRUVICA® treatment and dose modification.

Second Primary Malignancies - Other malignancies (range, 5 to 14%) including non-skin carcinomas (range, 1 to 3%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4 to 11%).

Tumor Lysis Syndrome -  Tumor lysis syndrome has been reported with IMBRUVICA® therapy. Monitor patients closely and take appropriate precautions in patients at risk for tumor lysis syndrome (e.g. high tumor burden).

Embryo-Fetal Toxicity -  Based on findings in animals, IMBRUVICA® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA®. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS

The most common adverse reactions (≥25%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia* (57%, 52%, 43%), neutropenia* (47%, 51%, 44%), diarrhea (51%, 48%, 37%), anemia* (41%, 36%, 13%), fatigue (41%, 28%, 21%), musculoskeletal pain (37%, 28%, NA), bruising (30%, 12%, 16%), nausea (31%, 26%, 21%), upper respiratory tract infection (34%, 16%, 19%), and rash (25%, 24%, 22%).

*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

Includes multiple ADR terms.

Not applicable; no associated ADRs.

The most common Grade 3 or 4 non-hematological adverse reactions (≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse events.

Approximately 5% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse events. Most frequent adverse events leading to discontinuation were infections, subdural hematomas, and diarrhea in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors - Avoid co-administration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA® dose.

CYP3A Inducers - Avoid co-administration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment - Avoid use in patients with moderate or severe baseline hepatic impairment.  In patients with mild impairment, reduce IMBRUVICA® dose.

Please review the full Prescribing Information.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088).

Indications

IMBRUVICA® (ibrutinib) is indicated for the treatment of:

  • Patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
  • Patients with chronic lymphocytic leukemia (CLL) with 17p deletion.
  • Patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
    • Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
  • Patients with Waldenström's macroglobulinemia (WM)