Imbruvica (ibrutinib) is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, jointly developed and commercialized by Janssen and Pharmacyclics.

It is an oral therapy approved to be used, either alone or in combination with other therapies, for many B-cell non-Hodgkin’s lymphomas (NHL), including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL).

The treatment was also approved by the U.S Food and Drug Administration for chronic graft versus host disease (GvHD), which can develop following a transplant, and Waldenström’s macroglobulinemia, another type of NHL. Imbruvica has also been approved as a chemotherapy-free combination therapy with Rituxan (rituximab) to treat Waldenström’s macroglobulinemia.

Additionally, Imbruvica is being evaluated as a treatment for follicular lymphoma (FL).

How Imbruvica works

Treatments for lymphoma now include targeted therapies aimed at killing the type of cell that has turned cancerous or to stop signals that make cancerous cells grow, divide, and spread through the body. Targeted treatments can have fewer side effects since they may not affect other types of cells.

B-cell NHL originates in B-cells at the lymph nodes. B-cells are a type of immune system cell responsible for combating infections or threats by producing antibodies.

Imbruvica is a cell-signaling inhibitor that works by blocking the activity of BTK, a specific protein that is a part of a biologic pathway that helps B-cells stay alive and divide. By forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells, Imbruvica helps kill and reduce the number of cancerous B-cells. This stops or slows down the progression of cancer.

Imbruvica in clinical trials

Imbruvica was first evaluated in a Phase 1 dose-escalation trial (NCT00849654) to determine its maximum tolerable dose, safety, pharmacokinetics (movement in the body), pharmacodynamics (effect on the body), and tumor response. A total of 56 patients with various types of B-cell NHL were enrolled in the study. The results showed that Imbruvica was well-tolerated across various types of B-cell NHL.

The FDA approved Imbruvica in 2013 for the treatment of patients with MCL based on the results of an open-label Phase 2 trial (NCT01236391). During the trial, 111 patients who had received at least one prior therapy were given Imbruvica daily until their disease progressed or side effects became intolerable. The results showed that nearly 66% of participants saw their cancer shrink or disappear after treatment (called the overall response rate).

The FDA also approved Imbruvica for the treatment of CLL in 2013. The decision was based on the results of a Phase 1b/2 trial (NCT01105247), in which 85 patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) received Imbruvica. Results showed that nearly 58% of participants had their cancer shrink after treatment.

In 2015, the FDA approved Imbruvica as a first-line treatment for CLL based on the results of an open-label Phase 3 trial (NCT01722487). The trial compared the effect of Imbruvica to that of chemotherapy agent Leukeran (chlorambucil), and concluded that Imbruvica was superior to Leukeran in previously untreated patients with CLL or SLL.

In early 2017, the FDA approved Imbruvica as a first-line treatment specifically for relapsed/refractory MZL patients. The approval was based on data from an open-label, Phase 2 trial (NCT01980628) that evaluated the safety and effectiveness of Imbruvica in 63 MZL patients. The results showed meaningful tumor shrinkage, and the treatment was well-tolerated overall.

On Aug. 28, 2018, the FDA approved Imbruvica in combination with Rituxan as the first chemotherapy-free treatment for Waldenström’s macroglobulinemia. This was based on the results of a randomized, double-blind, placebo-controlled Phase 3 trial (NCT02165397) called iNNOVATE that took place at sites in North America, Europe, and Australia.

A total of 150 patients were assigned to receive either Imbruvica or a placebo daily, along with Rituxan weekly, for four weeks. After a three-month break, all patients received a weekly dose of Rituxan for another four weeks. Results, published in The New England Journal of Medicine, showed that, after 30 months, 82% of patients treated with the Imbruvica/Rituxan combination had no disease progression, compared with only 28% of patients in the placebo group.

Imbruvica is currently being tested in several other clinical trials for the treatment of various types of B-cell lymphomas alone or in combination with other treatments.

For example, a Phase 3 trial (NCT02947347)  is currently recruiting patients with FL that has not been previously treated. The purpose of this study is to evaluate whether the addition of Imbruvica to Rituxan will result in prolonging the length of time a patient lives with the disease, compared with Rituxan alone.

Other details

The most common side effects of Imbruvica are diarrhea, muscle and bone pain, rash, nausea, bruising, tiredness, and fever.


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