Kim Dong Hwan, Jung Hee Du, Kim Jong Gwang, Lee Je-Jung, Yang Deok-Hwan, Park Yeon Hee, Do Young Rok, Shin Ho Jin, Kim Min Kyoung, Hyun Myung Soo, Sohn Sang Kyun
Department of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Ilwon-dong 50, Kangnam-gu, Seoul, Korea 135-710.
Blood. 2006 Oct 15;108(8):2720-5. doi: 10.1182/blood-2006-01-009480. Epub 2006 Apr 11.
The precise mechanism of rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2-mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was also proposed as a mechanism of rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect rituximab's affinity for ADCC effector cells. The FCGR3A and FCGR2A gene polymorphisms were determined in DLBCL patients receiving R-CHOP (n = 113) compared with CHOP therapy (n = 85). The FCGR3A valine (V) allele was significantly correlated with a higher complete response rate to R-CHOP compared with the phenylalanine (F) allele (88% in V/V vs 79% in V/F vs 50% in F/F; P = .002), while no difference was found between FCGR2A polymorphisms. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of the FCGR3A gene polymorphism on response rate was not noted in the CHOP group. In terms of overall or event-free survival, no difference was found according to FCGR3A or FCGR2A alleles. The FCGR3A single nucleotide polymorphism (SNP) is predictive of response to R-CHOP, but does not correlate with survival in patients with DLBCL.
利妥昔单抗联合环磷酰胺/阿霉素/长春新碱/泼尼松（R-CHOP）治疗弥漫性大B细胞淋巴瘤（DLBCL）的确切机制尚未完全阐明。除了克服bcl-2介导的化疗耐药性外，由效应细胞通过免疫球蛋白G（IgG）片段C受体（FcRs）激活的抗体依赖性细胞毒性（ADCC）也被认为是利妥昔单抗的一种作用机制。本研究评估了FcR基因多态性对DLBCL患者R-CHOP治疗反应的影响，其依据是FcR基因多态性可影响利妥昔单抗对ADCC效应细胞的亲和力。对接受R-CHOP治疗的DLBCL患者（n = 113）和接受CHOP治疗的患者（n = 85）进行了FCGR3A和FCGR2A基因多态性检测。与苯丙氨酸（F）等位基因相比，FCGR3A缬氨酸（V）等位基因与R-CHOP治疗的更高完全缓解率显著相关（V/V为88%，V/F为79%，F/F为50%；P = .002），而FCGR2A基因多态性之间未发现差异。此外，V/V等位基因比其他等位基因反应达成更快。CHOP组未发现FCGR3A基因多态性对缓解率的影响。就总生存期或无事件生存期而言，根据FCGR3A或FCGR2A等位基因未发现差异。FCGR3A单核苷酸多态性（SNP）可预测对R-CHOP的反应，但与DLBCL患者的生存无关。
