Potential biomarkers of bortezomib activity in mantle cell lymphoma from the phase 2 PINNACLE trial.
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.
Goy
André
A
The Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601, USA. AGoy@humed.com
Bernstein
Steven H
SH
McDonald
Alice
A
Pickard
Michael D
MD
Shi
Hongliang
H
Fleming
Mark D
MD
Bryant
Barb
B
Trepicchio
William
W
Fisher
Richard I
RI
Boral
Anthony L
AL
Mulligan
George
G
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
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