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@article{1137476,
author = {Coiffier, Bertrand and Li, Weimin and Henitz, Erin D. and Karkera, Jayaprakash D. and Favis, Reyna and Gaffney, Dana and Shapiro, Alice and Theocharous, Panteli and Elsayed, Yusri A. and Velde, Helgi van de and Schaffer, Michael E. and Osmanov, Evgenii A. and Hong, Xiaonan and Scheliga, Adriana and Mayer, Jiří and Offner, Fritz and Rule, Simon and Teixeira, Adriana and RomejkoandJarosinska, Joanna and Vos, Sven de and Crump, Michael and Shpilberg, Ofer and Zinzani, Pier Luigi and Cakana, Andrew and Esseltine, DixieandLee and Mulligan, George and Ricci, Deborah},
article_location = {PHILADELPHIA},
article_number = {9},
doi = {http://dx.doi.org/10.1158/1078-0432.CCR-12-3069},
keywords = {INTERNATIONAL PROGNOSTIC INDEX; NON-HODGKIN-LYMPHOMA; INDOLENT LYMPHOMA; MULTIPLE-MYELOMA; LEUKEMIA-CELLS; KAPPA-B; R-CHOP; PROTEASOME; GENE; PHASE-2},
language = {eng},
issn = {1078-0432},
journal = {Clinical Cancer Research},
title = {Prespecified Candidate Biomarkers Identify Follicular Lymphoma Patients Who Achieved Longer Progression-Free Survival with Bortezomib-Rituximab Versus Rituximab},
volume = {19},
year = {2013}
}
TY - JOUR
ID - 1137476
AU - Coiffier, Bertrand - Li, Weimin - Henitz, Erin D. - Karkera, Jayaprakash D. - Favis, Reyna - Gaffney, Dana - Shapiro, Alice - Theocharous, Panteli - Elsayed, Yusri A. - Velde, Helgi van de - Schaffer, Michael E. - Osmanov, Evgenii A. - Hong, Xiaonan - Scheliga, Adriana - Mayer, Jiří - Offner, Fritz - Rule, Simon - Teixeira, Adriana - Romejko-Jarosinska, Joanna - Vos, Sven de - Crump, Michael - Shpilberg, Ofer - Zinzani, Pier Luigi - Cakana, Andrew - Esseltine, Dixie-Lee - Mulligan, George - Ricci, Deborah
PY - 2013
TI - Prespecified Candidate Biomarkers Identify Follicular Lymphoma Patients Who Achieved Longer Progression-Free Survival with Bortezomib-Rituximab Versus Rituximab
JF - Clinical Cancer Research
VL - 19
IS - 9
SP - 2551-2561
EP - 2551-2561
PB - American Association for Cancer Research
SN - 10780432
KW - INTERNATIONAL PROGNOSTIC INDEX
KW - NON-HODGKIN-LYMPHOMA
KW - INDOLENT LYMPHOMA
KW - MULTIPLE-MYELOMA
KW - LEUKEMIA-CELLS
KW - KAPPA-B
KW - R-CHOP
KW - PROTEASOME
KW - GENE
KW - PHASE-2
N2 - Purpose: Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. Experimental Design: A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. Results: In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11AGallele, low CD68 expression (<= 50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Conclusions: Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab.
ER -
COIFFIER, Bertrand, Weimin LI, Erin D. HENITZ, Jayaprakash D. KARKERA, Reyna FAVIS, Dana GAFFNEY, Alice SHAPIRO, Panteli THEOCHAROUS, Yusri A. ELSAYED, Helgi van de VELDE, Michael E. SCHAFFER, Evgenii A. OSMANOV, Xiaonan HONG, Adriana SCHELIGA, Jiří MAYER, Fritz OFFNER, Simon RULE, Adriana TEIXEIRA, Joanna ROMEJKO-JAROSINSKA, Sven de VOS, Michael CRUMP, Ofer SHPILBERG, Pier Luigi ZINZANI, Andrew CAKANA, Dixie-Lee ESSELTINE, George MULLIGAN a Deborah RICCI. Prespecified Candidate Biomarkers Identify Follicular Lymphoma Patients Who Achieved Longer Progression-Free Survival with Bortezomib-Rituximab Versus Rituximab. \textit{Clinical Cancer Research}. PHILADELPHIA: American Association for Cancer Research, 2013, roč.~19, č.~9, s.~2551-2561. ISSN~1078-0432. Dostupné z: https://dx.doi.org/10.1158/1078-0432.CCR-12-3069.
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