title: 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-kappaB p65 and low PSMA5 expression demonstrated a trend for better response and were significantly associated with longer time to progression; elevated NF-kappaB 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.
authors.affiliation: The Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601, USA. AGoy@humed.com
authors.forename: André
authors.initials: A
authors.lastname: Goy
authors.forename: Steven H
authors.initials: SH
authors.lastname: Bernstein
authors.forename: Alice
authors.initials: A
authors.lastname: McDonald
authors.forename: Michael D
authors.initials: MD
authors.lastname: Pickard
authors.forename: Hongliang
authors.initials: H
authors.lastname: Shi
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
authors.forename: Barb
authors.initials: B
authors.lastname: Bryant
authors.forename: William
authors.initials: W
authors.lastname: Trepicchio
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Boral
authors.forename: George
authors.initials: G
authors.lastname: Mulligan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001897:Boronic Acids; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011719:Pyrazines; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000069286:Bortezomib; C088874:PSMB5 protein, human; D046988:Proteasome Endopeptidase Complex