What Is Known about the Clinical and Economic Burden of Refractory Chronic Lymphocytic Leukemia in Clinical Practice: A Review of the Literature.
Authors: Thompson Gwilym J , Lévy Vincent , Payne Krista , Wasiak Radek , Lis Yvonne 
Published: October 2019

Abstract
Abstract 4549

Introduction
Chronic lymphocytic leukemia (CLL) is the most common adult haematological malignancy in the Western world. It remains incurable and follows an extremely variable clinical course with survival ranging from months to decades. In those who become refractory to fludarabine based therapy, median survival is less than 1 year.

Methods
To identify data related to the clinical and economic sequelae of patients in routine clinical care diagnosed with refractory CLL, a systematic literature search of MEDLINE and EMBASE was conducted for the period January 1999-July 2009. The search terms used included incidence, prevalence, natural history, characteristics, clinical management, clinical outcomes, use of health care resources and was focused on patients with fludarabine refractory CLL also refractory to alemtuzumab (fludarabine and alemtuzumab refractory) or less suitable for alemtuzumab due to bulky lymph nodes (bulky fludarabine refractory). Supplementary checks were made of reference lists, particularly in review articles. Relevant conference proceedings for the period January 2006-July 2009 were also examined.

Results
The search of MEDLINE and EMBASE identified 102 articles of which 26 reported on the more general populations of patients with haematological malignancies, 61 on CLL and 15 on refractory CLL. Of those articles reporting data in relation to CLL (n=61), 49 described patient characteristics and outcomes, prognostic factors, diagnostic and treatment options, natural history of the disease, epidemiology, patient management and specific treatment outcomes and 12 review articles addressed areas such as prognostic factors and treatment options. Of those reporting on refractory CLL (n=15), one was a review article of novel agents and 14 were studies evaluating outcomes following salvage treatment with various pharmaceutical agents and other therapeutic interventions but mainly in patients refractory to fludarabine. Only one US study had evaluated patients who were refractory to both fludarabine and alemtuzumab or were bulky fludarabine refractory, examining response and survival following a variety of salvage treatments (Tam et al. Leukemia and Lymphoma 2007;48:1931-9). The search of conference proceedings identified 27 abstracts, 19 of which evaluated patients with CLL reporting on a range of topics including natural history and survival, prognostic factors and outcomes achieved with existing and experimental pharmaceutical interventions. Only two abstracts specifically reported on patients who were refractory to both fludarabine and alemtuzumab or were bulky fludarabine refractory, examining response rates following administration of a novel pharmaceutical agent (European Haematology Association Meeting 2009, abstracts 0494 and 0919).

Conclusions
There is very little data from clinical practice on clinical outcomes and none on economic sequelae for patients with double refractory or bulky nodal refractory disease. The lack of such data is likely to hinder the achievement of better outcomes for patients and the evaluation of cost effectiveness for newer agents. This lack of data to inform clinical practice and decision making has prompted the initiation of an observational study in five European countries with the objectives of characterising the current patterns of care, survival outcomes and resource utilization in double refractory and bulky nodal refractory CLL patients in Europe. The study, based on a retrospective chart review of approximately 250 patients, is currently underway in France, Germany, Italy, Spain and the UK. It is anticipated that the results, planned to be available by the end of 2009, will help to identify unmet clinical needs, quantify the clinical and economic burden in this particular population and contribute to the development of new treatment guidelines.

Disclosures:
Lévy: GlaxoSmithKline: Consultancy. Payne:GlaxoSmithKline: Consultancy. Wasiak:GlaxoSmithKline: Consultancy. Lis:GlaxoSmithKline: Consultancy.