Bartlett Nancy L, Hahn Uwe, Kim Won-Seog, Fleury Isabelle, Laribi Kamel, Bergua Juan-Miguel, Bouabdallah Krimo, Forward Nicholas, Bijou Fontanet, MacDonald David, Portell Craig A, Ghesquieres Herve, Nowakowski Grzegorz, Yasenchak Christopher A, Patterson Monica, Ho Linda, Rustia Evelyn, Fanale Michelle, Jie Fei, Kim Jeong-A
Division of Oncology, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO.
Haematology Unit, Royal Adelaide Hospital, Adelaide, Australia.
J Clin Oncol. 2025 Mar 20;43(9):1061-1072. doi: 10.1200/JCO-24-02242. Epub 2025 Jan 7.
In patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), brentuximab vedotin (BV) as monotherapy or combined with either lenalidomide (Len) or rituximab (R) has demonstrated efficacy with acceptable safety. We evaluated the efficacy and safety of BV + Len + R versus placebo + Len + R in patients with R/R DLBCL.
ECHELON-3 is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial comparing BV + Len + R with placebo + Len + R in patients with R/R DLBCL. Patients received BV or placebo once every 3 weeks, Len once daily, and R once every 3 weeks. The primary end point was overall survival (OS), and secondary end points included investigator-assessed progression-free survival (PFS) and objective response rate (ORR). A prespecified interim analysis was performed after 134 OS events, with two-sided = .0232 as the efficacy boundary.
Patients (N = 230) were randomly assigned to receive BV + Len + R (n = 112) or placebo + Len + R (n = 118). Two patients in the placebo arm did not receive treatment. With a median follow-up of 16.4 months, the median OS was 13.8 months with BV + Len + R versus 8.5 months with placebo + Len + R (hazard ratio, 0.63 [95% CI, 0.45 to 0.89]; two-sided = .009). The median PFS was 4.2 months with BV + Len + R versus 2.6 months with placebo + Len + R (hazard ratio, 0.53 [95% CI, 0.38 to 0.73]; two-sided < .001). The ORR was 64% ([95% CI, 55 to 73]; two-sided < .001) with BV + Len + R and 42% (95% CI, 33 to 51) with placebo + Len + R; complete response rates were 40% and 19%, respectively. Treatment-emergent adverse events (AEs) occurred in 97% of patients in both arms. In both arms, the most common treatment-emergent AEs were neutropenia, thrombocytopenia, diarrhea, and anemia.
BV + Len + R demonstrated a statistically significant survival benefit with a manageable safety profile in heavily pretreated patients with R/R DLBCL.
在复发或难治性（R/R）弥漫性大B细胞淋巴瘤（DLBCL）患者中，单药使用维布妥昔单抗（BV）或联合来那度胺（Len）或利妥昔单抗（R）已显示出疗效且安全性可接受。我们评估了BV + Len + R与安慰剂 + Len + R在R/R DLBCL患者中的疗效和安全性。
ECHELON - 3是一项随机、双盲、安慰剂对照、多中心3期试验，比较BV + Len + R与安慰剂 + Len + R在R/R DLBCL患者中的疗效。患者每3周接受一次BV或安慰剂，每天一次Len，每3周一次R。主要终点是总生存期（OS），次要终点包括研究者评估的无进展生存期（PFS）和客观缓解率（ORR）。在134例OS事件发生后进行了预先指定的中期分析，将双侧α = 0.0232作为疗效边界。
患者（N = 230）被随机分配接受BV + Len + R（n = 112）或安慰剂 + Len + R（n = 118）。安慰剂组有2例患者未接受治疗。中位随访16.4个月，BV + Len + R组的中位OS为13.8个月，而安慰剂 + Len + R组为8.5个月（风险比，0.63 [95% CI，0.45至0.89]；双侧P = 0.009）。BV + Len + R组的中位PFS为4.2个月，而安慰剂 + Len + R组为2.6个月（风险比，0.53 [95% CI，0.38至0.73]；双侧P < 0.001）。BV + Len + R组的ORR为64%（[95% CI，55至73]；双侧P < 0.001），安慰剂 + Len + R组为42%（95% CI，33至51）；完全缓解率分别为40%和19%。两组中97%的患者发生了治疗中出现的不良事件（AE）。在两组中，最常见的治疗中出现的AE是中性粒细胞减少、血小板减少、腹泻和贫血。
在经过大量治疗的R/R DLBCL患者中，BV + Len + R显示出具有统计学意义的生存获益，且安全性可控。
