Nowicka, Malgorzata, Hilton, Laura K., Ashton-Key, Margaret, Hargreaves, Chantal E, Lee, Chern, Foxall, Russell, Carter, Matthew, 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, Trněný, Marek, Rushton, Christopher K., Slack, Graham W., Farinah, Pedro, Strefford, Jonathan C., Oestergaard, Mikkel Z., Morin, Ryan D. and Cragg, Mark (2021) Prognostic significance of FCGR2B expression for the response of DLBCL patients to rituximab or obinutuzumab treatment. Blood Advances, 5 (15), 2945-2957. (doi:10.1182/bloodadvances.2021004770).
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 FCGR2B messenger 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 FCGR2B expression 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 FCGR2B expression favored G-CHOP over R-CHOP was observed (HR, 0.67; 95% CI, 0.44-1.02; P = .0622); however, low FCGR2B expression favored R-CHOP (HR, 1.58; 95% CI, 1.00-2.50; P = .0503). In Arthur and GOYA, FCGR2B expression 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/FCGR2B expression has prognostic value in R-treated patients with DLBCL and may confer differential responsiveness to R-CHOP/G-CHOP.
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