Rituximab for Chronic Lymphocytic Leukemia in Treatment-Naïve and Treatment-Experienced Patients

Ann Janssens, MD; Robin Foa, MD; Michael J. Keating, MD, BS; Iain Tatt, PhD; and Emma S. C. Carr, BSc, MSc, PhD
Published: Monday, Jan 23, 2012

Abstract

There has been a lack of meta-analyses and systematic reviews conducted in chronic lymphocytic leukemia (CLL). Structured searches were conducted in publication and conference databases to identify randomized controlled trials (RCTs) that are reporting efficacy data for treatment-naïve CLL and both RCTs and non-RCTs for relapsed/refractory CLL. Eight RCTs met prespecified inclusion criteria to permit a meta-analysis of fludarabine/cyclophosphamide/rituximab (FCR) with alemtuzumab, bendamustine, chlorambucil, fludarabine, and fludarabine/cyclophosphamide (FC). A mixed treatment comparison demonstrated that FCR significantly prolonged progression-free survival (PFS) compared with all other treatments (hazard ratios, 0.24-0.56) and significantly increased overall response rate (ORR) compared with all other treatments. FCR significantly increased the complete response (CR) rate compared with chlorambucil, fludarabine, and FC (odds ratios of 30.3, 10.1, and 2.7, respectively). For relapsed and refractory CLL, 9 RCTs and 86 non-RCTs were identified that reported efficacy data. A meta-analysis was deemed inappropriate due to trial heterogeneity. Overall, overall survival (OS) and PFS ranged from 24 to 33.8 months and from 6 to 30.6 months, respectively, depending on the therapy. Across all trials, FCR showed the greatest improvement in PFS, with robust ORR and CR rates. The identified studies indicated that FCR is highly efficacious for the treatment of both untreated and relapsed/refractory patients with CLL. These studies and the benefit of FCR are largely applicable to young and fit patients with CLL, and the best treatment for older patients could not be extracted from this analysis. Going forward, this evidence-based review should be updated with longer follow-up from trials to better determine OS benefit.

Introduction Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world, with an incidence rate of approximately 3.9 per 100,000 persons per year.1 Approximately 14,570 patients will be diagnosed with CLL in the United States in 2011.2 Primarily a malignancy of the elderly, the median age at diagnosis is 72 years in the United States, and approximately 70% of patients are aged >65 years.3 The disease is largely characterized by a slow, often asymptomatic progression over several years as malignant cells gradually accumulate in the blood, bone marrow, and lymph nodes.4 Anemia, thrombocytopenia, and immunosuppression can accompany painless lymph node enlargement and organomegaly. Systemic symptoms, such as fever, sweating, and weight loss, may be rare. Patients with early disease are usually left untreated; however, most patients will eventually require treatment.5
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