학술논문
Prognostic significance of FCGR2Bexpression for the response of DLBCL patients to rituximab or obinutuzumab treatment
Document Type
Article
Author
Nowicka, Malgorzata; Hilton, Laura K.; Ashton-Key, Margaret; Hargreaves, Chantal E.; Lee, Chern; Foxall, Russell; Carter, Matthew J.; Beers, Stephen A.; Potter, Kathleen N.; Bolen, Christopher R.; Klein, Christian; Knapp, Andrea; Mir, Farheen; Rose-Zerilli, Matthew; Burton, Cathy; Klapper, Wolfram; Scott, David W.; Sehn, Laurie H.; Vitolo, Umberto; Martelli, Maurizio; Trneny, Marek; Rushton, Christopher K.; Slack, Graham W.; Farinha, Pedro; Strefford, Jonathan C.; Oestergaard, Mikkel Z.; Morin, Ryan D.; Cragg, Mark S.
Source
Blood Advances; August 2021, Vol. 5 Issue: 15 p2945-2957, 13p
Subject
Language
ISSN
24739529; 24739537
Abstract
Fc γ receptor IIB (FcγRIIB) is an inhibitory molecule capable of reducing antibody immunotherapy efficacy. We hypothesized its expression could confer resistance in patients with diffuse large B-cell lymphoma (DLBCL) treated with anti-CD20 monoclonal antibody (mAb) chemoimmunotherapy, with outcomes varying depending on mAb (rituximab [R]/obinutuzumab [G]) because of different mechanisms of action. We evaluated correlates between FCGR2Bmessenger RNA and/or FcγRIIB protein expression and outcomes in 3 de novo DLBCL discovery cohorts treated with R plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) reported by Arthur, Schmitz, and Reddy, and R-CHOP/G-CHOP-treated patients in the GOYA trial (NCT01287741). In the discovery cohorts, higher FCGR2Bexpression was associated with significantly shorter progression-free survival (PFS; Arthur: hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.01-1.19; P= .0360; Schmitz: HR, 1.13; 95% CI, 1.02-1.26; P= .0243). Similar results were observed in GOYA with R-CHOP (HR, 1.26; 95% CI, 1.00-1.58; P= .0455), but not G-CHOP (HR, 0.91; 95% CI, 0.69-1.20; P= .50). A nonsignificant trend that high FCGR2Bexpression favored G-CHOP over R-CHOP was observed (HR, 0.67; 95% CI, 0.44-1.02; P= .0622); however, low FCGR2Bexpression favored R-CHOP (HR, 1.58; 95% CI, 1.00-2.50; P= .0503). In Arthur and GOYA, FCGR2Bexpression was associated with tumor FcγRIIB expression; correlating with shorter PFS for R-CHOP (HR, 2.17; 95% CI, 1.04-4.50; P= .0378), but not G-CHOP (HR, 1.37; 95% CI, 0.66-2.87; P= .3997). This effect was independent of established prognostic biomarkers. High FcγRIIB/FCGR2Bexpression has prognostic value in R-treated patients with DLBCL and may confer differential responsiveness to R-CHOP/G-CHOP.