Chronic Lymphocytic Leukaemia (CLL) is the most common leukaemia in adults in the Western world and is diagnosed in approximately 5 persons per 100,000 population per year.
Whereas many cancers are associated with rapid proliferation of tumour cells, in contrast CLL is largely a disease of gradual “accumulation”, where the leukaemic cells have a profoundly prolonged life-span.
The mechanism underlying this is an escape from the normal process of physiologic programmed cell death, or apoptosis.
The B-cell lymphoma-2 (BCL-2) gene and the derived protein, and related members of the larger family of BCL-2 proteins which share the common “BH3”-binding element in their structure are the regulators of this process of apoptosis and it has long been known that CLL cells over-express this pro-survival BCL-2 protein.
An oral drug, ABT-199/GDC-0199 was designed to exclusively mimic the binding of this “BH3” structural element exclusively to the BCL-2 protein, hence the drug class designation of “BH3-mimetic”.
This action restores the regulatory process that tells cancer cells to self-destruct.
The drug is jointly developed by AbbVie and Genentech and is being investigated in a repertoire of studies from phase-I single agent, combination with anti-CD20 monoclonal antibodies and standard chemotherapy, and is in phase-II and –III studies in CLL.
The presentation updated the results of the CLL arm of the ongoing phase-I single-agent study and established;
Details of these issues were presented by Professor John Seymour (Peter MacCallum Cancer Centre, Australia).
Source: EHA