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.

1st Department of Medicine 1st Faculty of Medicine Charles University General Hospital Prague Czech Republic

Antibody and Vaccine Group Centre for Cancer Immunology School of Cancer Sciences University of Southampton Faculty of Medicine University of Southampton Southampton United Kingdom

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

Department of Pathology and Tumor Biology Nagoya Graduate School of Medicine Nagoya University Nagoya Japan

Department of Translational and Precision Medicine Section of Hematology Sapienza University Rome Italy

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; and

Royal Marsden Hospital London United Kingdom

School of Cancer Sciences Faculty of Medicine University of Southampton Southampton United Kingdom

Southampton Cancer Research United Kingdom Experimental Cancer Medicines Centre University of Southampton Southampton United Kingdom

Southampton University Hospitals National Health Service Foundation Trust Southampton United Kingdom

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ClinicalTrials.gov
NCT01332968, NCT01287741