Title: Venetoclax in combination with rituximab for treating relapsed or refractory chronic lymphocytic leukaemia [ID1097]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of venetoclax in combination with rituximab within its marketing authorisation for treating relapsed or refractory chronic lymphocytic leukaemia.

Lay abstract: Chronic lymphocytic leukaemia (CLL) is a malignant disorder of white blood cells (lymphocytes). It causes anaemia, swollen lymph nodes, spleen enlargement, weight loss and increased susceptibility to infection. People with CLL may live with a considerable burden of symptoms impacting on their quality of life whether or not they have received treatment. CLL is a common form of leukaemia, with an estimated 3,515 new diagnoses in England each year (1). The risk of developing CLL increases with age and is more common in men (2). Median survival ranges from about 3 to 12 years depending on the genetic subtype and the stage at which the disease is diagnosed. Approximately 5% to 10% of people diagnosed with CLL are considered to have ‘high-risk’ disease. The British Committee for Standards in Haematology (BCSH) defines people with ‘high risk’ as those with previously untreated or relapsed CLL associated with a 17p deletion or TP53 mutation (the presence of 17p deletion or TP3 mutation influences the rate of cell growth as well as the resistance of the disease to treatment) and who require treatment, and those whose disease (regardless of biomarkers being present) relapses within 2 years of, or is refractory to purine analogue based chemotherapies (for example fludarabine)(3),(4). The BCSH defines relapse as disease progression at least 6 months after achieving a complete response or partial response. Refractory disease is defined as treatment failure or disease progression within 6 months of therapy. Treatment options for relapsed CLL vary depending on factors such as performance status, co-morbidities and previous treatments. NICE technology appraisal guidance 487 recommends venetoclax for use within the Cancer Drugs Fund as an option for treating CLL in adults whose disease has progressed after both chemo-immunotherapy and a B-cell receptor pathway inhibitor. NICE technology appraisal guidance 429 recommends ibrutinib alone as an option for treating CLL in adults who have had at least 1 prior therapy. NICE technology appraisal guidance 359 recommends idelalisib in combination with rituximab for CLL in adults when the disease has been treated but has relapsed within 24 months. NICE technology appraisal guidance 193 recommends fludarabine, cyclophosphamide and rituximab (FCR) as an option for people with relapsed or refractory CLL unless their disease is refractory to fludarabine or has been previously treated with rituximab. References 1. Cancer Research UK (2014) Chronic lymphocytic leukaemia incidence statistics. Accessed December 2017. 2. Cancer Research UK (2015) Chronic lymphocytic leukaemia risks and causes. Accessed December 2017. 3. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia (2012). British Committee for Standards in Haematology. Accessed December 2017. 4. BCSH CLL guidelines interim statement 2015. Accessed December 2017.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS