Targeted treatment and new agents in follicular lymphoma.

Follicular lymphomas are indolent diseases, which, while highly responsive to chemotherapy, remain incurable. Various combinations of standard chemotherapy drugs have not improved the outcome. The availability of effective and well-tolerated monoclonal antibodies (MoAbs), such as rituximab, provided the first evidence that new agents could prolong the survival of these patients. An increasing number of effective drugs are now being evaluated either as single agents or in combinations. These include chemotherapy drugs, bendamustine and bortezomib, MoAbs, other agents that inhibit various cellular pathways including spleen tyrosine kinase, mammalian target of rapamycin, PI3-kinase and apoptosis, and drugs that target the tumor microenvironment, such as the immunomodulatory agent lenalidomide. Rational development of combination strategies, including correlative studies to enhance our understanding of the mechanisms of action and resistance of the drugs, and the biology of the tumor, will continue to improve the outcome of patients with follicular lymphoma.