Prognostic significance of FCGR2B expression for the response of DLBCL patients to rituximab or obinutuzumab treatment
| Autor: | Christopher Rushton, Wolfram Klapper, Jonathan C. Strefford, Cathy Burton, Mark S. Cragg, Ryan D. Morin, Stephen A. Beers, Andrea Knapp, Malgorzata Nowicka, Christopher R. Bolen, Chern Lee, Chantal E. Hargreaves, Laura K. Hilton, Pedro Farinha, Matthew J. Carter, Margaret Ashton-Key, Matthew J. J. Rose-Zerilli, Kathleen N. Potter, Graham W. Slack, Maurizio Martelli, Christian Klein, Mikkel Z. Oestergaard, Umberto Vitolo, Laurie H. Sehn, Farheen Mir, Marek Trneny, Russell Foxall, David W. Scott |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Vincristine medicine.medical_specialty Cyclophosphamide FCGR2B Antibodies Monoclonal Humanized 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine immune system diseases Obinutuzumab Chemoimmunotherapy Prednisone hemic and lymphatic diseases Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Lymphoid Neoplasia business.industry Receptors IgG Hematology Prognosis medicine.disease Lymphoma 030104 developmental biology chemistry 030220 oncology & carcinogenesis Rituximab Lymphoma Large B-Cell Diffuse business medicine.drug |
| Zdroj: | Blood Adv |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2021004770 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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