The drug ibrutinib was well tolerated and highly effective in patients with untreated, relapsed and unresponsive chronic lymphocytic leukemia—leading to large reductions in tumor burden, according to the results of a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2013, held in Washington, D.C., April 6-10.
Chronic lymphocytic leukemia (CLL) 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 is 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.
Although there are effective treatments for CLL, some populations are harder to treat and tend to have worse outcomes. Many elderly patients are unable to tolerate current aggressive standard treatments. Also, individuals with a deletion in the short arm of chromosome 17 (referred to as “del 17p) have poor outcomes with chemotherapy.
Ibrutinib is a selective inhibitor of Bruton’s tyrosine kinase, a component of the B-cell receptor signaling pathway that plays a key role in the development and progression of CLL. In other words, the targeted therapy attacks the pathway that mediates disease progression.
To evaluate the efficacy of ibrutinib, researchers conducted a phase II single-center study that included 53 patients—24 who were age 65 and older and 29 with the del 17p mutation. Patients received 420 mg of ibrutinib daily. Researchers evaluated response to the drug after 6 months and again every 6 months until the disease progressed.
At six months, there were 44 evaluable patients—54 percent of patients with del 17p mutation had a partial response, as did 55 percent of patients in the elderly cohort. Ninety-five percent of patients showed at least a 50 percent reduction in lymph node disease, and all showed reduction in spleen enlargement, with a median reduction of 55 percent. Tumor infiltration in bone marrow biopsies fell by a median of 82%, and the median absolute lymphocyte count fell by a median of 62%. At 12 months, the estimated progression-free survival was 94 percent. Ibrutunib was well tolerated. Most adverse events were mild and included diarrhea, fatigue, and rash.
The researchers concluded that ibrutinib was highly effective in patients with untreated, relapsed and unresponsive CLL, regardless of their del 17p status.
Wiestner A, Herman S, Mustafa R, et al. Potent single agent activity of Ibrutinib (PCI-32765) in patients with chronic lymphocytic leukemia (CLL): clinical and translational results from an ongoing phase II study. Presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10. Abstract LB-141.
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