Drugs in Clinical Development for Chronic Lymphocytic Leukaemia: Summary and Table
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ADIS PROFILE SUMMARY
Drugs in Clinical Development for Chronic Lymphocytic Leukaemia: Summary and Table
Ó Springer International Publishing Switzerland 2015
Chronic lymphocytic leukaemia (CLL) is a type of nonHodgkin lymphoma that results from the transformation of B-lymphocytes in the bone marrow into leukaemia cells. These cells divide more rapidly than normal cells and do not undergo the usual apoptotic processes that destroy older cells, causing a gradual increase in the number of malignant lymphocytes, which eventually leave the bone marrow and accumulate in the peripheral blood and lymph nodes. CLL is the most commonly diagnosed adult leukaemia in western countries, with an estimated 4.5 new cases per 100,000 men and women per year in the US (based on population data from 2008 to 2012). In the early stages of the disease, many people with CLL are asymptomatic and do not require treatment, but instead undergo regular monitoring to detect when the disease progresses to an advanced stage where treatment is warranted. Until recently, the standard treatment for these later stages of CLL was centred on chemotherapy using cytotoxic drugs and biologicals, such as the combination of fludarabine, cyclophosphamide and rituximab, or chlorambucil, to destroy the abnormal cancer cells. Such treatments did not cure the disease but rather aimed to keep the disease in remission, reducing levels of malignant lymphocytes to enable the bone marrow to function normally. However, as with many chemotherapy regimens, such treatment is hard on the body and is often
not viable for older, frail patients. Given that CLL is typically a disease of older adults, with the average age of first diagnosis being 72 years, this represented a significant unmet need for the majority of patients with CLL. Fortunately, recent progress in the development and approval of targeted therapies that block specific molecular pathways inside the cancer cells, such as Pharmacyclics’ Imbruvica (ibrutinib),which targets a protein called Bruton’s agammaglobulinaemia tyrosine kinase (BTK), and Gilead’s Zydelig (idelalisib), which inhibits phosphatidylinositol-3 (PI3) kinase, and immunotherapies that help the immune system by flagging cancer cells for destruction, such as Genmab’s Arzerra (ofatumumab) and Genentech’s Gazyva (obinutuzumab), often given in combination with chemotherapy, are translating into impressive gains for patients. The development pipeline for CLL is also quite exciting, with multiple treatments showing early signs of efficacy, including follow-on BTK and PI3 kinase inhibitors and drugs with novel mechanisms of action such as those targeting the Bcl-2 protein, which regulates programmed cell death and therefore plays a key role in keeps malignant lymphocytes alive.Table 1 provides a list of experimental drugs, drug combinations and vaccines currently under investigation for the treatment of chronic lymphocytic leukaemia.
Ascerta Pharma Pharmacopeia
Intellikine
Celgene Corporation
Acalabrutinib (ACP-196)
Dinaciclib (MK 7965, PS 095760,
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