A systematic review and network meta-analysis to evaluate the comparative efficacy of interventions for unfit patients with chronic lymphocytic leukemia

Städler, N., Shang, A., Bosch, F., Briggs, A. , Goede, V., Berthier, A., Renaudin, C. and Leblond, V. (2016) A systematic review and network meta-analysis to evaluate the comparative efficacy of interventions for unfit patients with chronic lymphocytic leukemia. Advances in Therapy, 33(10), pp. 1814-1830. (doi: 10.1007/s12325-016-0398-2) (PMID:27535291)

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Introduction: Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in ‘unfit’ (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients. Methods: For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm. A manual review, validated by external experts, of all studies that met at least one of these criteria was also performed to confirm that they evaluated first-line therapeutic options for unfit patients with CLL. Results: In unfit patients, the main NMA (five studies for PFS and four for OS) demonstrated clear preference in terms of PFS for obinutuzumab + chlorambucil (G-Clb) versus rituximab + chlorambucil (R-Clb), ofatumumab + chlorambucil (O-Clb), fludarabine and chlorambucil (median hazard ratios [HRs] 0.43, 0.33, 0.20, and 0.19, respectively), and a trend for better efficacy versus rituximab + bendamustine (R-Benda) and RFC-Lite (median HR 0.81 and 0.88, respectively). OS results were generally consistent with PFS data, (median HR 0.48, 0.53, and 0.81, respectively) for G-Clb versus Clb, O-Clb, and R-Clb 0.35 and 0.81 versus F and R-Benda, respectively); however, the OS findings were associated with higher uncertainty. Treatment ranking reflected improved PFS and OS with G-Clb over other treatment strategies (median rank of one for both endpoints). Conclusion: G-Clb is likely to show superior efficacy to other treatment options selected in our NMA for unfit treatment-naïve patients with CLL.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Briggs, Professor Andrew
Authors: Städler, N., Shang, A., Bosch, F., Briggs, A., Goede, V., Berthier, A., Renaudin, C., and Leblond, V.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Health Economics and Health Technology Assessment
Journal Name:Advances in Therapy
Publisher:Springer Verlag
ISSN (Online):1865-8652
Published Online:17 August 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Advances in Therapy 33(10):1814-1830
Publisher Policy:Reproduced under a Creative Commons License

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