Bendamustine in non-Hodgkin lymphoma: the double-agent that came from the Cold War

Bendamustine was first synthesized in the early 1960s at the Institute for Microbiology and Experimental Therapy in Jena, East Germany by Ozegowski and Krebs. The molecule, originally termed IMET 3393 (4-[5-(bis[2-chloroethyl]amino)-1-methyl-2-benzimidazolyl] butyric acid), was intended to be a "bi-functional" molecule with alkylator and antimetabolite properties. Extensive studies were conducted using this compound over a 20-year period in East Germany, and it became a highly used chemotherapeutic agent in the eastern block before the fall of the Iron Curtain. After its licensing in Europe in the mid 1990s, more than 18,000 patients were studied using this compound, principally in Germany. Over the past decade, significant interest has been generated as a result of ongoing studies that have demonstrated the unique antitumor properties of this compound as a single agent and in different combinations. This article provides a review of studies using bendamustine in the treatment of non-Hodgkin lymphomas.