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

Abstract

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.).

• Authors: Farrukh T Awan, Neil E Kay, Melanie E Davis, Wenting Wu, Susan M Geyer, Nelson Leung, Diane F Jelinek, Renee C Tschumper, Charla R Secreto, Thomas S Lin, Michael R Grever, Tait D Shanafelt, Clive S Zent, Timothy G Call, Nyla A Heerema, Gerard Lozanski, John C Byrd, David M Lucas
• Journal: Blood (Blood) Vol. 113 Issue 3 Pg. 535-7 (Jan 15 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19008456 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Biomarkers, Tumor
• Myeloid Cell Leukemia Sequence 1 Protein
• Proto-Oncogene Proteins c-bcl-2
• Pentostatin
• Rituximab
• Cyclophosphamide

Topics

• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (analysis)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Humans
• Kaplan-Meier Estimate
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, metabolism, mortality)
• Myeloid Cell Leukemia Sequence 1 Protein
• Pentostatin (administration & dosage)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rituximab
• Treatment Outcome