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Marginal Zone Lymphoma (MZL)

Indication1

 

MZL

IMBRUVICA® (ibrutinib) is indicated for the treatment of patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.

Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Reference:

1. IMBRUVICA® (ibrutinib) Prescribing Information. Pharmacyclics LLC. 2017.

 

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IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA®. Grade 3 or higher bleeding events (intracranial hemorrhage [including 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 and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA® for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections - Fatal and nonfatal infections have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA®. Evaluate patients for fever and infections and treat appropriately.

Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 13%) based on laboratory measurements occurred in patients treated with single agent 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, hypertension, 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. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA® treatment and follow dose modification guidelines.

Hypertension - Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA® with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA®. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies - Other malignancies (range, 3% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2% to 13%).

Tumor Lysis Syndrome - Tumor lysis syndrome has been infrequently reported with IMBRUVICA® therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

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® and for 1 month after cessation of therapy. 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. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) in the clinical trial were thrombocytopenia*, fatigue (44%), anemia*, diarrhea (43%), bruising** (41%), musculoskeletal pain** (40%), hemorrhage** (30%), rash** (29%), nausea (25%), peripheral edema  (24%), arthralgia (24%), cough (22%), neutropenia*, upper respiratory tract infection (21%), dyspnea (21%).

The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) were pneumonia** (10%), fatigue (6%), diarrhea (5%), rash** (5%), and hypertension** (5%). Treatment emergent Grade 3 or 4 neutropenias (13%), anemia (13%), and thrombocytopenias (6%) were reported in patients.

Nine percent of patients discontinued treatment due to adverse reactions in the WM (6%) and MZL (13%) trials. For MZL, the most common (≥2 subjects) adverse reactions leading to treatment discontinuation were diarrhea, interstitial lung disease**, and rash** (3% each). Adverse reactions leading to dose reduction occurred in 10% of MZL patients.

*Treatment-emergent decreases (all grades) of platelets (49%), hemoglobin (43%), and neutrophils (22%) were based on laboratory measurements.
**Includes multiple ADR terms

DRUG INTERACTIONS

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

CYP3A Inducers - Avoid coadministration 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 the IMBRUVICA® dose.

Please see full Prescribing Information.

Indication

IMBRUVICA® (ibrutinib) is a kinase inhibitor indicated for the treatment of patients with:

  • Marginal zone lymphoma (MZL) who require systemic therapy and have
    received at least one prior anti-CD20-based therapy 

    • Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 


© Pharmacyclics LLC. 2017

© Janssen Biotech, Inc. 2017

07/17 PRC-02355