New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals

Abstract

Leukemia and lymphoma are systemic malignancies that represent half of all childhood cancers, though 90% occur in adults. Various treatment options are available, but therapy is mainly systemic chemotherapy plus appropriate monoclonal antibodies. In certain situations radiotherapy and bone marrow transplantation play a role. Some types/subtypes of these diseases are potentially curable, yet many leukemias and lymphomas do not properly respond to current therapies. Although the FDA (US Food and Drugs Administration) approvals of new drugs have shown a small increasing trend between 2007-2012, overall, the trend of new approvals remains relatively steady between 2006-2013, with a peak of 39 new drugs approved in 2012 and a drop in the new FDA drug approvals in 2013, to 27. Drugs approved for cancer treatment have shown a similar trend. Between 2006-2013, at least one drug was approved every year for the treatment of particular types of lymphoma or leukemia, except in 2010, with a peak of 5 new approvals in 2012. Between January 2013-March 2014, several important new approvals were made: ibrutinib for the treatment of CLL and mantle cell lymphoma (MCL), obinutuzumab for the treatment of CLL (in combination with chlorambucil), and lenalidomide for the treatment of mantle cell lymphoma. The results, importance, adverse effects and mechanisms of action of these agents are discussed in this review. These results held promise and their discovery and approval for the treatment of CLL and MCL is a major step forward. However, the emergence of resistance and the lack of cures need to be addressed by rational development of combination therapy, as well as development of novel drugs with enhanced potency or different mechanism of action, to achieve better overall and complete response rates with decreased toxicity.