在美国一项随机II期组间研究ECOG-ACRIN E1412中，来那度胺添加至R-CHOP方案可改善新诊断弥漫性大B细胞淋巴瘤的预后。

Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412.

作者信息

Nowakowski Grzegorz S, Hong Fangxin, Scott David W, Macon William R, King Rebecca L, Habermann Thomas M, Wagner-Johnston Nina, Casulo Carla, Wade James L, Nagargoje Gauri G, Reynolds C M, Cohen Jonathon B, Khan Nadia, Amengual Jennifer E, Richards Kristy L, Little R F, Leonard John P, Friedberg Jonathan W, Kostakoglu Lale, Kahl Brad S, Witzig Thomas E

机构信息

Division of Hematology, Mayo Clinic, Rochester, MN.

Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA.

出版信息

J Clin Oncol. 2021 Apr 20;39(12):1329-1338. doi: 10.1200/JCO.20.01375. Epub 2021 Feb 8.

PURPOSE

Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell-like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL.

PATIENTS AND METHODS

Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS).

RESULTS

Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell-like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% ( = .06) and 73% ( = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided = .1.

CONCLUSION

In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL.

目的

来那度胺联合利妥昔单抗加环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）（R2CHOP）用于未经治疗的弥漫性大B细胞淋巴瘤（DLBCL）已显示出有前景的活性，尤其是在活化B细胞样（ABC）亚型中。东部肿瘤协作组（ECOG）-ACRIN试验E1412是一项随机II期研究，比较R2CHOP与R-CHOP用于未经治疗的DLBCL。

患者与方法

新诊断的DLBCL患者，II期大包块-IV期疾病，国际预后指数（IPI）≥2，且ECOG体能状态≤2符合入组条件，并按1:1随机分配接受R2CHOP或R-CHOP治疗六个周期。使用NanoString Lymph2Cx对肿瘤进行细胞起源分析。主要终点是所有患者的无进展生存期（PFS），共同主要终点是ABC-DLBCL患者的PFS。次要终点包括总缓解率（ORR）、完全缓解（CR）率和总生存期（OS）。

结果

共纳入349例患者；280例患者（145例R2CHOP和135例R-CHOP）可评估：94例为ABC-DLBCL，122例为生发中心B细胞样-DLBCL，18例无法分类，46例情况不明。两组间基线特征均衡，中位年龄为66岁（范围24-92岁）；70%的患者为IV期疾病；分别有34%、43%和24%的患者IPI为2、3以及4或5。骨髓抑制在R2CHOP组更常见。R-CHOP组的ORR和CR率分别为92%和68%，R2CHOP组分别为97%（P = 0.06）和73%（P = 0.43）。中位随访时间为3.0年；与R-CHOP相比，R2CHOP使疾病进展或死亡风险降低34%（风险比[HR]，0.66；95%CI，0.43至1.01），3年PFS为73%对61%，单侧P = 0.03，且OS有所改善（3年时分别为83%和75%；HR，0.67；单侧P = 0.05）。ABC-DLBCL患者中R2CHOP的PFS HR为0.67，单侧P = 0.1。