General Information

Imbruvica (ibrutinib) is an orally available, selective inhibitor of Bruton's tyrosine kinase (Btk), a gene that is disrupted in the human disease X-linked agammaglobulenemia (XLA). BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways.

Imbruvica is specifically approved for mantle cell lymphoma in patients who have received at least one prior therapy.

Imbruvica is supplied as a capsule for oral administration. The recommended dose is 560 mg taken orally once daily (four 140 mg capsules once daily), taken with water.

Clinical Results

FDA Approval
The FDA approval of Imbruvica was based on an open-label, multi-center, single-arm trial of 111 previously treated subjects. The median age was 68 years. The subjects received Imbruvica orally at 560 mg 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). The ORR was 69% and the median time to response was 1.9 months.

Side Effects

Adverse events associated with the use of Imbruvica may include, but are not limited to, the following:

• thrombocytopenia
• diarrhea
• neutropenia
• anemia
• fatigue
• musculoskeletal
• pain
• peripheral edema
• upper respiratory tract infection
• nausea
• bruising
• dyspnea
• constipation
• rash
• abdominal pain
• vomiting
• decreased appetite

Mechanism of Action

Imbruvica (ibrutinib) is an orally available, selective inhibitor of Bruton's tyrosine kinase (Btk). Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK’s crole in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion.

Literature References

Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. New England Journal of Medicine 2013 Aug 8;369(6)

Additional Information

For additional information regarding Imbruvica or mantle cell lymphoma, please visit the Imbruvica web page.