Imbruvica® Effective in Newly Diagnosed & Recurrent Chronic Lymphocytic Leukemia

FDA Expands Approval of Imbruvica® to Include Initial Treatment for Chronic Lymphocytic Leukemia & Small Cell Lymphoma

by Dr. C.H.Weaver M.D. updated 3/2019

Imbruvica (ibrutinib) produces long-lasting anti-cancer responses and prolongs survival among patients with newly diagnosed chronic lymphocytic leukemia (CLL), as well as those who have received prior therapies and may be used as a single agent or in combination with other therapy.

About Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia is the most common form of adult leukemia. The American Cancer Society estimates that approximately 15,000 people will be diagnosed with CLL this year. Currently, there are approximately 95,000 people in the United States living with CLL.

CLL and small lymphocytic lymphoma (SLL) are characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells that exist in two forms: B- and T-cells. These cells are produced in the bone marrow and each serves a specific function in aiding the body to fight infection. The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal. B-lymphocytes accumulate in the blood, bone marrow, lymph nodes, and spleen. This results in overcrowding of these areas and suppression of the formation and function of blood and immune cells. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further reduction in the body’s ability to fight infection.

CLL and SLL are diagnosed most commonly in elderly patients (65 years or greater). Since these patients are often unable to tolerate aggressive therapies compared to their younger counterparts due to additional medical conditions and/or differences in the metabolizing of the agents, the toxicity of treatment is an important issue.

About Imbruvica

Imbruvica is a first-in-class oral agent that inhibits the activity of Bruton’s tyrosine kinase (BTK). Within CLL/SLL cells, BTK is a protein/carbohydrate complex that is involved in maintaining cellular survival and replication. By inhibiting the activity of BTK, ibrutinib reduces the growth of cancer and causes cellular death. Ibrutinib is approved for the treatment of CLL, and continues to be studied in different types of cancers.

What Does the Research Show?

Imbruvica as Initial Therapy

The U.S. Food and Drug Administration (FDA) has approved IMBRUVICA® in combination with Gazyva (obinutuzumab) for treatments of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). (1)

The FDA approval was based on results from the Phase 3 iLLUMINATE clinical trial which compared Gazyva administered with either Imbruvica or chlorambucil in 212 adult patients. The overall response rate was 89% in the Imbruvica treated patients compared to only 73% in the chlorambucil group. Treatment with Imbruvica + Gazyva also led to a significant delay in cancer progression. Chlorambucil treated patients survived an average of 19 months without cancer Imbruvica treated patients’ experienced a 77 percent reduction in the risk of cancer progression or death compared to those treated with chlorambucil.

Imbruvica as a single agent – and now as a combination with Gazyva – provides patients with CLL with an alternative to frontline treatment with chemoimmunotherapy.

Promising Activity of Imbruvica Plus Rituxan in High-Risk CLL.

Researchers from MD Anderson Cancer Center recently reported in the journal TheLancet Oncology that the combination of Imbruvica® and Rituxan® (rituximab) showed promising activity in the management of patients with high-risk CLL.(2)

In this clinical trial, 40 adult patients with high-risk CLL were enrolled and treated with a combination of Imbruvica and Rituxan. High risk was defined as having either a high-risk cytogenetic abnormalities; (deletion 17p, TP53 mutation, or deletion 11q) or shortened time to CLL progression (< 36 months) after initial first-line treatment.

Overall 95% of patients had a response to treatment with Imbruvica and Rituxan and 87% had partial and 8% had complete disappearance of their CLL following treatment. Consistent with previous reports, the treatment was generally well tolerated. Overall 78% of high risk patients treated with the combination of Imbruvica and Rituxan survived without evidence of CLL progression 18-months from treatment.

Imbruvica in Previously Treated CLL Patients

Researchers have reported data from two different large clinical trials (the RESONATE and RESONATE-2 trials) in an attempt to determine the effectiveness of Imbruvica in different lines of therapy among patients with CLL.

Some patients had not received prior therapy to Imbruvica (referred to as treatment naïve or TN), while other patients had received at least one prior therapy before starting treatment with ibrutinib (referred to as previously treated or PT). Patients with the del17p mutation were not included in this analysis.

  • At 2 years, the median survival time without progression of disease, as well as the median overall survival time had not yet been reached for either TN or PT patients.
  • Patients treated with a greater number of prior therapies before receiving ibrutinib had an increased likelihood of discontinuing ibrutinib due to disease progression, compared to those who had received 0-1 prior therapies before receiving ibrutinib.
  • Among patients who discontinued treatment with ibrutinib, those who received 0-1 prior therapies have not yet reached median overall survival following discontinuation of ibrutinib; however, those who received 2 or more prior therapies had a median overall survival of 7-9 months following discontinuation of ibrutinib.
  • Side effects of ibrutinib were comparable between TN and PT patients.
  • Anti-cancer responses with ibrutinib were high, despite the number of prior therapies received.

The researchers concluded that Imbruvica produced favorable anti-cancer responses, survival without progression of cancer, and overall survival among patients with CLL, regardless of the number of prior therapies. However, patients who had received 0-1 prior therapies were less likely to experience cancer progression on Imbruvica, and demonstrated an improved survival following discontinuation of Imbruvica, compared to those who received 2 or more prior therapies.


  1. Burger J, Ketaing M, Wierda W, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. The Lancet Oncology, 15;1090 – 1099, September 2014.
  2. O’Brien S, Byrd J, Hillmen P, et al. Outcomes with ibrutinib by line of therapy in patients with CLL: Analyses from phase III data. Proceedings from 2016 ASCO. Abstract # 7520. Available at: . Accessed June 29, 2016.

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