Immunomodulatory Agents in Follicular Lymphoma

Hematol Oncol Clin North Am. 2020 Aug;34(4):715-726. doi: 10.1016/j.hoc.2020.02.007. Epub 2020 Apr 8.


New treatment strategies in follicular lymphoma (FL) are driven by a deeper understanding of microenvironmental cues supporting lymphomagenesis, chemoresistance, and immuno-escape. These immune-mediated signaling pathways contribute to initial learnings and clinical successes with lenalidomide, the first, oral, non-chemotherapeutic immunomodulatory drug, combined with anti-CD20 antibodies. This combination of lenalidomide with rituximab showed similar efficacy to chemoimmunotherapy (CIT) in first-line patients requiring therapy, and is approved in relapsed/refractory FL. We review the biology supporting the rationale for adequate inhibitory receptor/ligand pathways targeting the tissue immune microenvironment of FL cells, and potential immunomodulating combinations to replace CIT in the near future.

Keywords: Chemo-free approaches; Follicular lymphoma; Immunomodulatory agents; Monoclonal antibodies; Tumor immune microenvironment.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Immunological Synapses / drug effects
  • Immunomodulation / drug effects*
  • Lenalidomide / pharmacology
  • Lenalidomide / therapeutic use
  • Lymphoma, Follicular / diagnosis
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / etiology
  • Lymphoma, Follicular / mortality
  • Molecular Targeted Therapy
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Immunologic Factors
  • Lenalidomide