What is Ibrutinib (Imbruvica)?

From the Guidelines

Ibrutinib is a highly effective treatment option for patients with Waldenström's macroglobulinemia, with an overall response rate of 91% and a major response rate of 73%, as demonstrated in a prospective study of 63 symptomatic patients 1. The typical dose of ibrutinib is 420 mg taken once daily, and it works by blocking Bruton's tyrosine kinase (BTK), an enzyme that helps abnormal B cells survive and multiply. Some key points to consider when prescribing ibrutinib include:

• Monitoring for treatment-related toxic effects, such as neutropenia, thrombocytopenia, and atrial fibrillation, which were reported in a study of 63 symptomatic patients with WM 1
• Informing patients about the potential for increased risk of bleeding and the importance of avoiding grapefruit products and Seville oranges while taking ibrutinib
• Regularly monitoring blood pressure, as hypertension can occur, and being aware of the potential for grade 3 atrial fibrillation and hypertension, which were reported in 9% and 6% of patients, respectively, in a phase III randomized study 1 The use of ibrutinib as a single agent has been shown to be effective and well-tolerated in patients with relapsed/refractory WM, with high rates of response and durability of responses, as demonstrated in studies by Treon et al and Dimopoulos et al 1. It's also important to note that ibrutinib has been shown to significantly improve overall response rate, progression-free survival, and overall survival compared to ofatumumab in patients with relapsed/refractory CLL/SLL, as demonstrated in a phase III randomized study 1.

From the FDA Drug Label

The safety and effectiveness of IMBRUVICA in combination with chemoimmunotherapy were assessed but have not been established based on an open-label, randomized study (NCT02703272) in 35 patients, which included 26 pediatric patients age 5 to less than 17 years, with previously treated mature B-cell non-Hodgkin lymphoma. The safety and effectiveness of IMBRUVICA in pediatric patients have not been established in CLL/SLL, CLL/SLL with 17p deletion, or WM. Adults and children 1 year of age and older with chronic graft versus host disease (cGVHD) after failure of 1 or more lines of systemic therapy. It is not known if IMBRUVICA is safe and effective in children under 1 year of age

• Ibrutinib is used to treat various conditions, including chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), and chronic graft versus host disease (cGVHD) in adults and children 1 year of age and older.
• The safety and effectiveness of ibrutinib have not been established in pediatric patients with certain conditions, such as CLL/SLL, CLL/SLL with 17p deletion, or WM.
• Children under 1 year of age should not be given ibrutinib, as its safety and effectiveness in this age group are unknown 2, 2.

From the Research

Ibrutinib Overview

• Ibrutinib is a Bruton's tyrosine kinase inhibitor used in the treatment of relapsed or refractory mantle cell lymphoma and chronic lymphocytic leukemia 3, 4, 5, 6
• It was granted accelerated approval by the US Food and Drug Administration in November 2013 for mantle cell lymphoma and in February 2014 for chronic lymphocytic leukemia 3, 6

Efficacy

• In a phase 2 study of 111 patients with relapsed or refractory mantle cell lymphoma, the overall response rate was 68% and the median progression-free survival was 13.9 months 3
• In a phase 3 trial (RESONATE) comparing ibrutinib and ofatumumab for the treatment of relapsed and refractory chronic lymphocytic leukemia, ibrutinib demonstrated a significantly higher overall response rate (43% vs 4%) and improved overall survival at 12 months (90% vs 81%) 3
• Ibrutinib has shown durable remission, improved progression-free survival, and overall survival in indolent B-cell lymphoid malignancies 3, 4, 5

Safety and Tolerability

• Ibrutinib was well tolerated, with no dose-limiting toxicity observed 3, 4, 5
• The most common adverse reactions included thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea 6
• In patients intolerant of ibrutinib, zanubrutinib, a next-generation BTK inhibitor, has been shown to be well tolerated and effective 7

Clinical Use

• Ibrutinib is an effective treatment modality as a salvage therapy for mantle cell lymphoma and chronic lymphocytic leukemia, particularly in older patients who are not candidates for intensive chemotherapy and/or those with del (17p) 3, 4, 5
• Current practice guidelines recommend ibrutinib as an upfront treatment option for patients with chronic lymphocytic leukemia and del (17p) 3