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 Blood, 15 January 2009, Vol. 113, No. 3, pp. 535-537.
Prepublished online as a Blood First Edition Paper on November 13, 2008; DOI 10.1182/blood-2008-08-173450.

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CLINICAL TRIALS AND OBSERVATIONS

Brief report

Mcl-1 expression predicts progression-free survival in chronic lymphocytic leukemia patients treated with pentostatin, cyclophosphamide, and rituximab

Farrukh T. Awan1, Neil E. Kay2, Melanie E. Davis1, Wenting Wu2, Susan M. Geyer2, Nelson Leung2, Diane F. Jelinek2, Renee C. Tschumper2, Charla R. Secreto2, Thomas S. Lin1, Michael R. Grever1, Tait D. Shanafelt2, Clive S. Zent2, Timothy G. Call2, Nyla A. Heerema2, Gerard Lozanski2, John C. Byrd1,*, and David M. Lucas1,*

1 The Ohio State University, Columbus; and 2 Mayo Clinic, Rochester, MN

Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic member of the Bcl-2 protein family. Increased Mcl-1 expression is associated with failure to achieve remission after treatment with fludarabine and chlorambucil in patients with chronic lymphocytic leukemia (CLL). However, the influence of Mcl-1 expression has not been examined in CLL trials using chemoimmunotherapy. We investigated Mcl-1 protein expression prospectively as part of a phase 2 study evaluating the efficacy of pentostatin, cyclophosphamide, and rituximab in patients with untreated CLL. No significant difference by Mcl-1 expression was noted in pretreatment or response parameters. However, in patients with higher Mcl-1 expression, both minimal residual disease-negative status and progression-free survival was found to be significantly reduced (57% vs 19%, P = .01; 50.8 vs 18.7 months; P = .02; respectively). Mcl-1 expression may therefore be useful in predicting poor response to chemoimmunotherapy. These findings further support pursuing treatment strategies targeting this important antiapoptotic protein. (Because the trials described were conducted before the requirement to register them was implemented, they are not registered in a clinical trial database.)


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