by Dr. C.H. Weaver M.D. 5/2019
An interim analyses of the phase 3 “ASCEND” clinical trial evaluating single-agent Calquence (acalabrutinib) compared to Rituxan (rituximab) plus idelasib or bendamustine in recurrent chronic lymphocytic leukemia (CLL) is closed early due to favorable results. (1)
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.
Calquence is a Bruton’s tyrosine kinase (BTK) inhibitor. 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, a BTK inhibitor reduces the growth of leukemia cells and causes cellular death. 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 Calquence may more selectively block the BTK pathway and avoid some known side effects.
Calquence is approved for the treatment of CLL, and continues to be studied in different types of cancers. Calquence has been included as a treatment option in the National Comprehensive Cancer Network (NCCN) CLL guidelines. (2,3,4)
The ASCEND clinical trial evaluated Calquence in 310 previously-treated patients with CLL. Patients were treated with either Calquence monotherapy or Rituxan (rituximab) plus physician’s choice of idelalisib or bendamustine and directly compared. Interim results show a significant and clinically-meaningful delay in progression of CLL with Calquence, full trial results will be published shortly.
Clinical results published in the New England Journal of Medicine initially demonstrated that acalabrutinib (ACP-196) was well tolerated and yielded high response rates that were durable in patients with chronic lymphocytic leukemia.
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.
- National Comprehensive Cancer Network (NCCN) chronic lymphocytic leukemia/small lymphocytic leukemia clinical practice guidelines. www.nccn.org. Accessed May 9, 2019.
- Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373:2425-2437
- No authors*.* First-line ibrutinib confirmed for CLL. Cancer Discov. 2019 Feb;9(2):OF4.
- Byrd JC, Harrington B, O’Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374:323-332.
- Patel V, Balakrishnan K, Bibikova E, et al. Comparison of acalabrutinib, a selective Bruton tyrosine kinase inhibitor, with ibrutinib in chronic lymphocytic leukemia cells. Clin Cancer Res. 2017;23:3734-3743