The New Landscape in CLL Novel Therapies
Dr. Francesco Forconi (MD, DM, PhD, FRCPath)Associate Professor in Haematological Oncology - Cancer Science Unit, University of Southampton.
Consultant Haematologist - Cancer Care, Haematology Department. Southampton University Hospital Trust.
Chronic lymphocytic leukaemia is a tumour of a type of white blood cells, named B-cells or B lymphocytes, circulating in blood, bone marrow and lymph nodes. These B-cells are defined by the expression of the ‘B-cell receptor’ (BCR). The BCR is a surface immunoglobulin which signals stimuli essential for the survival and proliferation of the tumour cells. New small molecules have now been developed as therapeutical drugs to prevent the tumour BCR from signalling those stimuli. These drugs are commonly called BCR-associated inhibitors, and the results in patients have demonstrated very high and protracted efficacy despite a very low toxicity profile. The results been so exciting, that approvals for commercialisation have been rapidly obtained in the United States and in Europe for the first-in-class compounds (Ibrutinib and idelalisib). However there are other new drugs that clinicians are testing in clinical trials as an alternative to conventional chemotherapy. Among them, inhibitors of molecules that prevent tumour cell death (BCL-2 inhibitors like GDC 0199) and new types of anti-CD20 monoclonal antibodies (obinutuzumab) seem very effective and are also awaited to be used in combinations outside clinical trials.