Clinical results published in the New England Journal of Medicine show that the new drug acalabrutinib (ACP-196) is well tolerated and yields high response rates that are durable in patients with chronic lymphocytic leukemia (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. The disease tends to get worse slowly.
ACP-196 is a Bruton’s tyrosine kinase (BTK) inhibitor. The drug works by permanently binding BTK, which is part of a chain of proteins that relays growth signals from the surface of CLL cells to genes in the cell nucleus enabling cancer cells to survive and grow. Drugs that block BTK stop the flow of these growth signals and the CLL cells die. Unlike Imbruvica™ (ibrutinib), the first BTK approved for the treatment of CLL, data reported from this study suggests that acalabrutinib may more selectively block the BTK pathway and avoid some known side effects.
Patients with CLL were enrolled in consecutive clinical trials evaluating different doses of acalabrutinib and followed for an average of 14.3 months from the initiation of treatment. Overall the researchers reported a response rate of 95 percent to treatment. Of the 61 patients who participated in this first-in-human testing of the agent, 87 percent were able to complete the trial treatment. No patients experienced Richter’s transformation, a rare condition where CLL morphs into an aggressive form of lymphoma, and only one patient’s cancer progressed.
Acalabrutinib appears promising and represents a new advancement in the management of CLL. Patients with CLL are benefiting from an expanding number of new drugs and treatment options in the past few years that provide hope in the overall management of this disease.
Reference: Byrd J, Harrington B, O’Brien S, et al. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. New England Journal of Medicine. December 7, 2015DOI: 10.1056/NEJMoa1509981.