Indication(s):

Treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Both indications are based on overall response rate. An improvement in survival or disease-related symptoms has not been established.

Pharmacology:

Ibrutinib is a small-molecule inhibitor of BTK. Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK’s role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. Nonclinical studies show that ibrutinib inhibits malignant B-cell proliferation and survival in vivo as well as cell migration and substrate adhesion in vitro.

Clinical Trials:

The safety and efficacy of Imbruvica in patients with MCL who have received at least one prior therapy were eva luated in an open-label, multi-center, single-arm trial of 111 previously treated patients. Imbruvica was administered orally at 560mg once daily until disease progression or unacceptable toxicity. Tumor response was assessed according to the revised International Working Group (IWG) for non-Hodgkin’s lymphoma (NHL) criteria. The primary endpoint in this study was investigator-assessed overall response rate (ORR).

Based on investigator assessment, results showed an ORR of 65.8% (95% CI: 56.2%, 74.5%) with a complete response (CR) in 17.1% and a partial response (PR) in 48.6%. The median duration of response (DOR) was 17.5 months (95% CI: 15.8, not reached). An Independent Review Committee (IRC) performed independent reading and interpretation of imaging scans. The IRC review demonstrated an ORR of 69%. The median time to response was 1.9 months.

The safety and efficacy of Imbruvica in patients with CLL who have received at least one prior therapy were eva luated in an open-label, multi-center trial of 48 previously treated patients. Imbruvica was administered orally at 420mg once daily until disease progression or unacceptable toxicity.

The ORR and DOR were assessed using a modified version of the International Workshop on CLL criteria by an IRC. The ORR was 58.3% (95% CI: 43.2%, 72.4%), all partial responses. None of the patients achieved a complete response. The DOR ranged from 5.6 to 24.2+ months. The median DOR was not reached.

Legal Classification:

Rx

Adults:

Swallow whole with water. MCL: 560mg once daily. CLL: 420mg once daily. Concomitant moderate CYP3A inhibitors: 140mg once daily. Dose modifications for toxicities: see full labeling.

Children:

Not established.

Warnings/Precautions:

Risk of hemorrhage; consider the benefit/risk of withholding treatment for 3–7 days pre-and post-surgery. Monitor for fever and infections; eva luate promptly if occurs. Monitor for myelosuppression; obtain CBCs monthly. Risk of second primary malignancies (eg, skin cancer or other carcinomas). Hepatic or renal impairment. Monitor creatinine levels periodically. Maintain adequate hydration. Pregnancy (Category D); avoid. Nursing mothers: not recommended.

Interaction(s)

Concomitant strong CYP3A inhibitors taken chronically (eg, ritonavir, indinavir, nelfinavir, saquinavir, boceprevir, telaprevir, nefazodone): not recommended; for short-term (≤7days) use of strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin); consider interrupting ibrutinib therapy. If concomitant moderate CYP3A inhibitors must be used (eg, fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, ciprofloxacin): reduce ibrutinib dose (see Adults). Avoid grapefruit and Seville oranges during treatment. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort); consider alternatives. Increased risk of hemorrhage with concomitant antiplatelets or anticoagulants.

Adverse Reaction(s)

Thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting, decreased appetite, pyrexia, arthralgia, stomatitis, sinusitis, dizziness.

How Supplied:

Caps—90, 120

LAST UPDATED:

3/3/2014