BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, British Columbia, Canada.
City of Hope, Duarte, CA.
J Clin Oncol. 2020 Jan 10;38(2):155-165. doi: 10.1200/JCO.19.00172. Epub 2019 Nov 6.
Patients with transplantation-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) fare poorly, with limited treatment options. The antibody-drug conjugate polatuzumab vedotin targets CD79b, a B-cell receptor component.
Safety and efficacy of polatuzumab vedotin with bendamustine and obinutuzumab (pola-BG) was evaluated in a single-arm cohort. Polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) was compared with bendamustine and rituximab (BR) in a randomly assigned cohort of patients with transplantation-ineligible R/R DLBCL (primary end point: independent review committee [IRC] assessed complete response [CR] rate at the end of treatment). Duration of response, progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods.
Pola-BG and pola-BR had a tolerable safety profile. The phase Ib/II pola-BG cohort (n = 27) had a CR rate of 29.6% and a median OS of 10.8 months (median follow-up, 27.0 months). In the randomly assigned cohort (n = 80; 40 per arm), pola-BR patients had a significantly higher IRC-assessed CR rate (40.0% 17.5%; = .026) and longer IRC-assessed PFS (median, 9.5 3.7 months; hazard ratio [HR], 0.36, 95% CI, 0.21 to 0.63; < .001) and OS (median, 12.4 4.7 months; HR, 0.42; 95% CI, 0.24 to 0.75; = .002; median follow-up, 22.3 months). Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% 33.3%), anemia (28.2% 17.9%), and thrombocytopenia (41% 23.1%), but similar grade 3-4 infections (23.1% 20.5%), versus the BR group. Peripheral neuropathy associated with polatuzumab vedotin (43.6% of patients) was grade 1-2 and resolved in most patients.
Polatuzumab vedotin combined with BR resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with BR in patients with transplantation-ineligible R/R DLBCL.
不适合移植的复发/难治性（R/R）弥漫性大 B 细胞淋巴瘤（DLBCL）患者预后较差，治疗选择有限。抗体药物偶联物 polatuzumab vedotin 靶向 CD79b，这是 B 细胞受体的一个组成部分。
在单臂队列中评估了 polatuzumab vedotin 联合苯达莫司汀和奥滨尤妥珠单抗（pola-BG）的安全性和疗效。在不适合移植的 R/R DLBCL 患者的随机分配队列中，比较了 polatuzumab vedotin 联合苯达莫司汀和利妥昔单抗（pola-BR）与苯达莫司汀和利妥昔单抗（BR）（主要终点：独立审查委员会[IRC]评估治疗结束时的完全缓解[CR]率）。使用 Kaplan-Meier 和 Cox 回归方法分析缓解持续时间、无进展生存期（PFS）和总生存期（OS）。
pola-BG 和 pola-BR 的安全性特征可接受。Ib/II 期的 pola-BG 队列（n=27）的 CR 率为 29.6%，中位 OS 为 10.8 个月（中位随访时间，27.0 个月）。在随机分配的队列中（n=80；每组 40 例），pola-BR 患者的 IRC 评估的 CR 率显著更高（40.0% vs. 17.5%；P=.026），IRC 评估的 PFS 和 OS 也更长（中位值分别为 9.5 个月 vs. 3.7 个月；HR，0.36，95%CI，0.21 至 0.63；P<.001；中位随访时间，22.3 个月）。pola-BR 患者的 3-4 级中性粒细胞减少症（46.2% vs. 33.3%）、贫血症（28.2% vs. 17.9%）和血小板减少症（41% vs. 23.1%）发生率较高，但 3-4 级感染率相似（23.1% vs. 20.5%）。与 BR 组相比，pola-BR 患者外周神经病变（43.6%的患者）为 1-2 级，且多数患者可缓解。
与 BR 相比，pola-BR 治疗不适合移植的 R/R DLBCL 患者，可显著提高 CR 率，并使死亡风险降低 58%。
