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Single-nucleotide Fcγ receptor polymorphisms do not impact obinutuzumab/rituximab outcome in patients with lymphoma
JC. Strefford, M. Nowicka, CE. Hargreaves, C. Burton, A. Davies, R. Ganderton, W. Hiddemann, C. Iriyama, W. Klapper, KV. Latham, M. Martelli, F. Mir, H. Parker, KN. Potter, MJJ. Rose-Zerilli, LH. Sehn, M. Trněný, U. Vitolo, CR. Bolen, C. Klein,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
A18087
Cancer Research UK - United Kingdom
A24721
Cancer Research UK - United Kingdom
A25139
Cancer Research UK - United Kingdom
A15581
Cancer Research UK - United Kingdom
NLK
Directory of Open Access Journals
od 2016
PubMed Central
od 2016
Europe PubMed Central
od 2016
ROAD: Directory of Open Access Scholarly Resources
od 2016
- MeSH
- folikulární lymfom * farmakoterapie MeSH
- humanizované monoklonální protilátky MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nukleotidy terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- receptory IgG * genetika MeSH
- rituximab terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Single-nucleotide polymorphisms (SNPs) have been shown to influence Fcγ receptor (FcγR) affinity and activity, but their effect on treatment response is unclear. We assessed their importance in the efficacy of obinutuzumab or rituximab combined with chemotherapy in untreated advanced follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in the GALLIUM (www.clinicaltrials.gov #NCT01332968) and GOYA (#NCT01287741) trials, respectively. Genomic DNA was extracted from patients enrolled in GALLIUM (n = 1202) and GOYA (n = 1418). Key germline SNPs, FCGR2A R131H (rs1801274), FCGR3A F158V (rs396991), and FCGR2B I232T (rs1050501), were genotyped and assessed for their impact on investigator-assessed progression-free survival (PFS). In both cohorts there was no prognostic effect of FCGR2A or FCGR3A. In FL, FCGR2B was associated with favorable PFS in univariate and multivariate analyses comparing I232T with I232I, with a more modest association for rituximab-treated (univariate: hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.54-1.14; P = .21) vs obinutuzumab-treated patients (HR, 0.56; 95% CI, 0.34-0.91; P = .02). Comparing T232T with I232I, an association was found for obinutuzumab (univariate: HR, 2.76; 95% CI, 1.02-7.5; P = .0459). Neither observation retained significance after multiple-test adjustment. FCGR2B was associated with poorer PFS in multivariate analyses comparing T232T with I232I in rituximab- but not obinutuzumab-treated patients with DLBCL (HR, 4.40; 95% CI, 1.71-11.32; P = .002; multiple-test-adjusted P = .03); however, this genotype was rare (n = 13). This study shows that FcγR genotype is not associated with response to rituximab/obinutuzumab plus chemotherapy in treatment-naive patients with advanced FL or DLBCL.
BC Cancer Centre for Lymphoid Cancer
Department of Hematopathology University of Kiel Kiel Germany
Department of Medicine 3 Ludwig Maximilians University Hospital Munich Munich Germany
Department of Medicine University of British Columbia Vancouver BC Canada
F Hoffmann La Roche Ltd Basel Switzerland
Genentech Inc South San Francisco CA
Haematological Malignancy Diagnostic Service Leeds Cancer Centre Leeds United Kingdom
Multidisciplinary Oncology Outpatient Clinic Candiolo Cancer Institute FPO IRCCS Candiolo Italy
Nuffield Department of Medicine John Radcliffe Hospital University of Oxford Oxford United Kingdom
Roche Innovation Center Zurich Roche Glycart AG Schlieren Switzerland
Royal Marsden Hospital London United Kingdom
School of Cancer Sciences Faculty of Medicine University of Southampton Southampton United Kingdom
Southampton University Hospitals National Health Service Foundation Trust Southampton United Kingdom
Citace poskytuje Crossref.org
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