Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Garth D. Nelson, Carrie A. Thompson, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, and Thomas E. Witzig, Mayo Clinic, Rochester, MN; Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, BC, Canada; Craig B. Reeder, Mayo Clinic, Scottsdale, AZ; and James M. Foran and Candido E. Rivera, Mayo Clinic, Jacksonville, FL.
J Clin Oncol. 2015 Jan 20;33(3):251-7. doi: 10.1200/JCO.2014.55.5714. Epub 2014 Aug 18.
Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL.
Eligible patients were adults with newly diagnosed untreated stages II to IV CD20(+) DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP.
In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively).
R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.
来那度胺在复发性弥漫性大 B 细胞淋巴瘤（DLBCL）中具有显著的单药活性。我们证明来那度胺可以与 R-CHOP（利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松）安全联合；这种新的组合称为 R2CHOP。本 II 期研究的目的是评估这种联合方案在新诊断的 DLBCL 中的疗效。
符合条件的患者为患有新诊断未经治疗的 II 期至 IV 期 CD20(+)DLBCL 的成年人。患者每天接受来那度胺 25mg 口服，第 1 天至第 10 天，每 21 天接受标准剂量 R-CHOP 治疗 6 个周期。所有患者在每个周期的第 2 天接受培非格司亭，并在整个治疗期间接受阿司匹林预防。在 R2CHOP 患者和来自 Lymphoma Database 的 87 名接受常规 R-CHOP 治疗的 DLBCL 对照患者中，通过肿瘤免疫组织化学确定 DLBCL 分子亚型，并分类为生发中心 B 细胞（GCB）与非 GCB。
共纳入 64 例 DLBCL 患者，60 例可评估疗效。总体缓解率为 98%（60 例中有 59 例），80%（60 例中有 48 例）达到完全缓解。24 个月时无事件生存和总生存（OS）率分别为 59%（95%CI，48%至 74%）和 78%（95%CI，68%至 90%）。在 R-CHOP 患者中，24 个月时无进展生存率（PFS）和 OS 分别为 28%和 64%（P<.001），非 GCB DLBCL 与 GCB DLBCL 分别为 46%和 78%（P<.001）。相比之下，根据非 GCB 和 GCB 亚型，R2CHOP 患者的 24 个月 PFS 或 OS 没有差异（2 年时分别为 60%和 59%[P=.83]和 83%和 75%[P=.61]）。
R2CHOP 在 DLBCL 中显示出有希望的疗效。来那度胺的加入似乎减轻了非 GCB 表型对患者结局的负面影响。
