Effect of FCGR2A and FCGR3A variants on CLL outcome

David Dornan, Olivia Spleiss, Ru Fang Yeh, Guillemette Duchateau-Nguyen, Annika Dufour, Jianguo Zhi, Tadeusz Robak, Sergey I. Moiseev, Anna Dmoszynska, Philippe Solal-Celigny, Krzysztof Warzocha, Javier Loscertales, John Catalano, Boris V. Afanasiev, Loree Larratt, Viktor A. Rossiev, Isabelle Bence-Bruckler, Christian H. Geisler, Marco Montillo, Michael K. WengerMartin Weisser

Research output: Contribution to journalArticleResearchpeer-review

53 Citations (Scopus)

Abstract

Polymorphisms of activating Fc-γ receptors (FCGRs) on natural killer cells and macrophages result in variable affinity for immunoglobulin G1 monoclonal antibodies and subsequently modulate antibody-dependent cellular cytotoxicity (ADCC) activity. Whether single-nucleotide polymorphisms of FCGRs correlate with survival of chronic lymphocytic leukemia (CLL) patients treated with a monoclonal antibody containing regimen is unclear. We assessed the FCGR3A and FCGR2A genotype of patients enrolled in the REACH trial, where patients received fludarabine and cyclophosphamide (FC) or rituximab plus FC (R-FC). FCGR3A and FCGR2A polymorphisms did not demonstrate prognostic significance in the FC arm (P = .42 and P = .64, respectively) or R-FC arm (P = .41 and P = .88, respectively) with respect to progression free survival. Patients with intermediate affinity genotypes (FV and HR) benefited significantly from addition of rituximab (hazard ratio = 0.55 [0.37-0.8 CI]; P = .0017 and hazard ratio = 0.63 [0.44-0.9 CI] ; P = .011, respectively). Similar benefit was suggested for patients with high-affinity VV and HH (hazard ratio = 0.86 [0.4-1.84 CI]; P = .7 and hazard ratio = 0.7 [0.41-1.18 CI] ; P = .18, respectively) and low-affinity FF and RR (hazard ratio = 0.85 [0.56-1.29 CI]; P = .44 and hazard ratio = 0.82 [0.47-1.42 CI] ; P = .48, respectively). Overall, our results suggest that FCGR2A and FCGR3A polymorphisms do not significantly influence the outcomes of relapsed or refractory CLL patients treated with FC or the monoclonal antibody regimen R-FC.
Original languageEnglish
Pages (from-to)4212-4222
Number of pages11
JournalBlood
Volume116
Issue number20
DOIs
Publication statusPublished - 18 Nov 2010

Cite this