Researchers from Ohio State University have reported that flavopiridol has “pronounced” activity in treating patients with relapsed chronic lymphocytic leukemia (CLL). The details of this study were presented at the 2008 meeting of the American Society of Clinical Oncology in Chicago May 30-June 2.¹

Flavopiridol is a cyclin-dependent kinase inhibitior that is being evaluated as a single agent and in combination with other agents for the treatment of CLL. Recent studies suggested that the efficacy of flavopiridol was schedule dependent and associated with the release of IL-6, which led to hyperacute tumor lysis syndrome. This led to the development of a regimen that consisted of a 30-minute loading dose followed by a four-hour infusion that was administered weekly for four to six weeks. The results of this study were published in 2007 in Blood.² The dose-limiting toxicity of this regimen was hyperacute tumor lysis syndrome due to cytokine release (IL-6), requiring aggressive prophylaxis and exclusion of patient with WBC counts >200,009/L. In this study 45% of 42 refractory patients achieved a partial response. These authors found significant activity of flavopiridol in patients with 17p13.1 cytogenetic abnormalities. These authors suggested that this agent is one of the most active agents in clinical trials for CLL.

At ASCO 2008, researchers reported data on 62 patients with relapsed CLL treated with flavopiridol. Patients in this study were pretreated with dexamethasone to block the effects of IL-6 release during therapy. All were treated with a 30-minute bolus infusion followed by a four-hour infusion. Six and a half percent had a complete response, and 42% a partial response. Responses were observed in 9/18 patients with adverse cytogenetics. These authors concluded that flavopiridol had “pronounced” activity in patients with relapsed CLL, including patients with bulky adenopathy and poor-risk cytogenetics.

Comments: It would appear from these data that flavopiridol will become a very useful agent for the treatment of CLL and possibly other low-grade lymphoid malignancies.

Reference:

¹ Lin TS, Andritsos LA, Fisher JB, et al. Activity of the cylin-dependent kinase (CPK) inhibitor flavopiridol in relapsed, genetically high risk chronic leukemia (CLL). Journal of Clinical Oncology. 2008;26:abstract 7007.

² Byrd JC, Lin TS, Dalton JT, et al. Flavorpiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood. 2007;109:399-404.