Chemotherapy-free treatment in patients with follicular lymphoma

Abstract

The outcome of patients with follicular lymphoma (FL) has improved over the last two decades through the introduction of anti-CD20 monoclonal antibodies, usually used in combination with chemotherapy. However, patients with FL still experience multiple relapses, requiring several lines of treatment. Early toxicity of chemotherapy is a significant concern and as the life expectancy of patients with FL is increasing, late toxicities become an increasingly important concern. Progress made in understanding the biology of FL, especially dysregulation of intracellular pathways and immunological antitumor responses, recently allowed for the development of innovative chemo-free therapeutic approaches. In this report, different options such as new anti-CD20 antibodies, antibodies targeting other cell surface antigens, bi-specific antibodies, immunomodulation, idiotype vaccine and other targeted therapies are presented. The article also highlights how, although promising in early phase studies, the cost–effectiveness of new agents will have to be justified in Phase III trials. Furthermore, chemo-free regimen might not mean toxicity-free treatment and monitoring of early and late toxicities is required.

Keywords:

• antitumor immune response
• follicular lymphoma
• immunomodulation
• monoclonal antibody
• rituximab
• targeted therapy

Financial & Competing Interests Disclosure

E Bachy is a consultant for Roche, while G Salles is a consultant for Roche, Celgene, Gilead and Janssen Pharmaceuticals. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Life expectancy of follicular lymphoma patients has increased with immuno-chemotherapy regimen. However, early and late toxicities of chemotherapy are a matter of concern.

• Recent advances have been made in the understanding of the lymphoma biology with deregulated cell signaling pathways and immunological antitumor response mechanisms. These have led to the rapid development of new agents: B-cell receptor pathway inihibitors targeting antibodies against various cell surface antigens or agents able to modulate the immune antitumor response.

• Second and third generations of anti-CD20 that might overcome rituximab resistance are now available. Some of them, such as GA101, present higher antibody-dependent cell cytotoxicity and others, such as ofatumumab, induce higher complement-dependent cytotoxicity.

• Other monoclonal antibodies targeting cell surface antigens such as CD22, CD37, CD74, CD80 are under development. Developing bispecific antibodies targeting two different cell surface antigens with a synergistic effect is another approach to improve efficacy. Some of them targeting CD19 and CD3 induce an expansion of T effector cells and improve the immune response against lymphoma.

• Besides the use of monoclonal antibodies that directly target the cell surface, another approach currently used is to foster the antitumor immune response with other monoclonal antibodies as anti-PD-1, anti-CTLA4 or anti-KIR.

Notes