Zhang Yian, Ren Yuhong, Zhuang Jingli, Yuan Ling, Wang Zhimei, Zhang Xuejiao, Wang Weiguang, Cheng Zhixiang, Cheng Luya, Li Jing, Liu Peng
Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, China.
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Cancer Med. 2025 Aug;14(16):e71162. doi: 10.1002/cam4.71162.
Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or are refractory to first-line treatment. This study aimed to determine the effectiveness and tolerability of the combination of Polatuzumab vedotin and Zanubrutinib plus Rituximab (Pola-ZR) or Obinutuzumab (Pola-ZG) in patients with relapsed/refractory (R/R) DLBCL.
We conducted a prospective observational study as part of our registered cohort study (NCT06203652). Patients were planned to receive six 21-day cycles of Pola-ZR/G, followed by Zanubrutinib monotherapy. The primary endpoint was to evaluate the best overall response rate (BOR), while secondary endpoints included the median progression-free survival (mPFS), safety, and complete response rate (CRR). We collected data from 73 R/R DLBCL patients who received traditional salvage therapies (TST). After propensity score matching, they were paired 1:1 with the Pola-ZR/G arm to compare the effectiveness and survival outcomes.
Twenty-two patients were enrolled (median age 68 years) in the Pola-ZR/G group. After a median follow-up of 16.1 months, the investigators assessed BOR; it was 70% (77.77% for Pola-ZR and 63.6% for Pola-ZG cohort), and CRR was 45% in 20 evaluable R/R patients. The mPFS was 8.3 months and was higher compared to the TST cohort. The median overall survival (OS) of the Pola-ZR/G cohort had not been reached at the time of analysis. The most common grade 3 to 4 adverse events were infections of all types and hematological toxicity.
In our study, patients derived clinical benefit after receiving Pola-ZR/G compared to TST; the regimens had a tolerable safety profile in patients with R/R DLBCL.
约30%的弥漫性大B细胞淋巴瘤（DLBCL）患者会复发或对一线治疗耐药。本研究旨在确定泊洛妥珠单抗维达替尼与泽布替尼加利妥昔单抗（Pola-ZR）或奥妥珠单抗（Pola-ZG）联合用药在复发/难治性（R/R）DLBCL患者中的有效性和耐受性。
作为我们注册队列研究（NCT06203652）的一部分，我们开展了一项前瞻性观察性研究。计划让患者接受六个21天周期的Pola-ZR/G治疗，随后接受泽布替尼单药治疗。主要终点是评估最佳总体缓解率（BOR），次要终点包括中位无进展生存期（mPFS）、安全性和完全缓解率（CRR）。我们收集了73例接受传统挽救性治疗（TST）的R/R DLBCL患者的数据。经过倾向评分匹配后，将他们与Pola-ZR/G组按1:1配对，以比较有效性和生存结果。
Pola-ZR/G组纳入了22例患者（中位年龄68岁）。中位随访16.1个月后，研究者评估了BOR；为70%（Pola-ZR队列77.77%，Pola-ZG队列63.6%），20例可评估的R/R患者的CRR为45%。mPFS为8.3个月，高于TST队列。分析时Pola-ZR/G队列的中位总生存期（OS）尚未达到。最常见的3至4级不良事件是各类感染和血液学毒性。
在我们的研究中，与TST相比，患者接受Pola-ZR/G治疗后获得了临床益处；这些方案在R/R DLBCL患者中具有可耐受的安全性。
