A network meta-analysis of progression free survival and overall survival in first-line treatment of chronic lymphocytic leukemia

Cancer Treat Rev. 2015 Feb;41(2):77-93. doi: 10.1016/j.ctrv.2014.11.004. Epub 2014 Dec 4.

Abstract

Background: A limited evidence exists regarding comparisons of clinical effectiveness of available therapies for first-line treatment of chronic lymphocytic leukemia (CLL).

Methods: We compared available therapies for treatment-naïve, symptomatic CLL regarding progression free survival (PFS) and overall survival (OS) in all the identified random control trials and in subgroups composed of younger/fit and older/unfit patients, using a Bayesian network meta-analysis.

Results: In younger/fit patients we obtained median of projected mean PFS of: 19, 26, 31, 43, 51 and 75months for chlorambucil, fludarabine, alemtuzumab, fludarabine with cyclophosphamide (FC), bendamustine and fludarabine with cyclophosphamide and rituximab (FCR), respectively. We noted median OS of: 59, 66, 66, 70months for FC, chlorambucil, FCR and fludarabine, respectively. In older/unfit patients we noted PFS of: 16, 17, 24, 30, 60months for chlorambucil, fludarabine and chlorambucil with ofatumumab (OClb) or rituximab (RClb) or obinutuzumab (GClb), respectively. We obtained median OS of: 44, 58, 59 and 90months for fludarabine, RClb, chlorambucil and GClb, respectively.

Conclusions: Our results suggest that: (1) FCR has higher potential of preventing CLL progression in younger/fit patients over four therapy options, which were subject of previous meta-analysis but also over bendamustine; (2) in these patients FCR does not entail prolonging of OS in comparison with chlorambucil and it is outperformed by fludarabine; (3) in older/unfit patients GClb demonstrates longer projected PFS than all assessed comparators; (4) in this group GClb has also the highest potential of increasing OS.

Keywords: B-cell; CLL; Chronic; Leukemia; Lymphocytic; Meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Alemtuzumab
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bayes Theorem
  • Bendamustine Hydrochloride
  • Chlorambucil / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality*
  • Markov Chains
  • Nitrogen Mustard Compounds / administration & dosage
  • Pentostatin / administration & dosage
  • Physical Fitness
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Rituximab
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Nitrogen Mustard Compounds
  • Chlorambucil
  • Pentostatin
  • Alemtuzumab
  • Rituximab
  • Cyclophosphamide
  • Bendamustine Hydrochloride
  • Vidarabine
  • ofatumumab
  • obinutuzumab
  • fludarabine