The role of chemotherapy in managing chronic lymphocytic leukemia: optimizing combinations with targeted therapy

Abstract

For many years, alkylating agents were the standard treatment for chronic lymphocytic leukemia (CLL). The advent of purine analogs improved response rates, but not overall survival, and although the monoclonal antibody rituximab is generally active against B-cell malignancies, it has demonstrated limited benefits as monotherapy for the treatment of CLL. However, specific combinations of chemotherapy, antibodies and targeted therapies have demonstrated additive or synergistic activity in CLL cells and deliver substantial clinical benefits. A greater understanding of the actions of chemotherapies and targeted agents on cellular pathways will advance the development of rationally designed combinations corresponding to individual patients’ disease profiles.

Keywords::

• chemoimmunotherapy
• chemotherapy
• chronic lymphocytic leukemia
• synergy
• targeted therapy

Financial & competing interests disclosure

This work was supported in part by CR Flowers’ Georgia Cancer Coalition Distinguished Scientist Award and Cancer Research Award, American Society of Hematology Amos Medical Faculty Development Award, National Cancer Institute R21 CA158686-01A1 and a Leukemia and Lymphoma Society Translational Research Award. LJ Nastoupil has received an honorarium from F. Hoffman-La Roche and is a consultant to Genentech/Roche. R Sinha has received research funding from Celgene. CR Flowers is a consultant to Celgene, Clinical Care Options, Genentech/Roche (unpaid), Millennium/Takeda (unpaid), Prescription Solutions, Seattle Genetics and Spectrum, and has received research funding from Abbott, Calistoga Pharmaceuticals, Celgene, Eastern Cooperative Oncology Group, Janssen Pharmaceuticals, Memorial Sloan–Kettering Cancer Center, Millennium/Takeda, National Cancer Institute, National Institute of Health, Northwestern University, Southwest Oncology Group and Spectrum. The authors were not compensated and retained full editorial control over the content of the paper. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing support was provided by Julie Ponting of Anthemis Consulting Ltd and was funded by Teva Pharmaceutical Industries, Frazer, PA, USA.