Flavopiridol Has Significant Activity in Relapsed Chronic Lymphocytic Leukemia

December 9, 2008

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 inhibitor 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.

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