Calquence Improves Survival in Relapsed Chronic Lymphocytic Leukemia
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
CLL is the most common type of leukemia in adults. (2) with an average age at the time of diagnosis being approximately 70 years of age. (3) In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets. This could result in anemia, infection and bleeding. B-cell receptor signaling through Bruton tyrosine kinase (BTK) is one of the essential growth pathways for CLL.
Within CLL cells, BTK is a protein/carbohydrate complex that is involved in maintaining cellular survival and replication. Inhibiting the activity of BTK reduces the growth of cancer cells and cause CLL cell death. Use of BTK inhibitors in the treatment of patients with CLL has become a standard treatment. Imbruvica (ibrutinib), is currently FDA-approved for both the first-line and subsequent treatment of patients with CLL with or without a 17p deletion, as well as other hematologic malignancies, including mantle cell lymphoma. Both Imbruvica and off-label use of Calquence are included as treatment options in the National Comprehensive Cancer Network (NCCN) CLL guidelines. (2,3,4)
Calquence is an inhibitor of Bruton tyrosine kinase. While the mechanisms of action of Imbruvica and Calquence are believed to be similar there is evidence that Calquence may be a more selective BTK inhibitor. Calquence is currently approved by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. (7,8)
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.
- National Comprehensive Cancer Network (NCCN) chronic lymphocytic leukemia/small lymphocytic leukemia clinical practice guidelines. 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.
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