Potential biomarkers of bortezomib activity in mantle cell lymphoma from the phase 2 PINNACLE trial

Abstract

Immunohistochemical analyses of archival tumor specimens were used for pre-planned exploratory analyses of protocol-specified candidate biomarkers of bortezomib activity in 73 patients with relapsed/refractory mantle cell lymphoma in the phase 2 PINNACLE study. Consistent with other studies, elevated Ki-67 was a marker of poor prognosis, demonstrating significant associations with shorter time to progression and overall survival. Elevated NF-κB p65 and low PSMA5 expression demonstrated a trend for better response and were significantly associated with longer time to progression; elevated NF-κB p65 demonstrated a trend toward longer overall survival. This is consistent with myeloma clinical genomics research, suggesting biomarker relevance across tumor types. Elevated p27 was significantly associated with longer overall survival. Overall survival analyses by International Prognostic Index and Mantle Cell Lymphoma International Prognostic Index confirmed differential prognosis by both scores. These biomarkers data begin to illuminate bortezomib's mechanism of action in lymphoma.

Keywords:

• Biomarkers
• bortezomib
• immunohistochemical analysis
• mantle cell lymphoma
• NF-κB p65

Acknowledgements

The authors would like to thank Laura Faron-Yowe, Aimy Tse, Nancy Goodman, and Jessica O'Keefe. The authors would also like to acknowledge the writing assistance of Steve Hill and Jane Saunders of FireKite during the development of this publication.

Declaration of interest: This research was supported by Millennium Pharmaceuticals, Inc., and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Development of this publication was funded by Millennium Pharmaceuticals, Inc.

A.M., M.D.P., H.S., B.B., W.T., A.L.B., and G.M. are or were employed by Millennium Pharmaceuticals, Inc. A.G., S.H.B., and R.I.F. have received honoraria from Millennium Pharmaceuticals, Inc., and S.H.B. and R.I.F. have acted as consultants for Millennium Pharmaceuticals, Inc.