基于奥妥珠单抗的联合方案治疗滤泡性淋巴瘤的单中心临床经验

Single-Center Clinical Experience with Obinutuzumab-Based Combination Regimens in the Treatment of Follicular Lymphoma

摘要: 目的：初步描述含奥妥珠单抗的联合方案治疗滤泡性淋巴瘤(FL)的单中心临床经验，并分析其疗效及安全性。方法：回顾性分析本中心16例FL患者(12例初诊，4例复发/难治性)接受含奥妥珠单抗的联合方案治疗后的疗效、无进展生存(PFS)和不良反应发生情况。结果：除1例因不良反应停用奥妥珠单抗无法评估疗效外，余15例患者采用含奥妥珠单抗的联合方案诱导治疗后客观缓解率及完全缓解率分别为86.7% (13/15)和73.3% (11/15)。中位随访27 (8~35)个月，1年和2年PFS分别为87.5%和68.9%。最常见的3~4级血液学毒性为中性粒细胞减少，贫血和血小板减少多为1~2级。外周血淋巴细胞亚群分析显示：与治疗前相比，CD4⁺ T细胞及CD19⁺ B细胞计数均在诱导治疗期间显著下降[0.181 (0.033~0.628) × 10⁹/L比0.506 (0.414~2.438) × 10⁹/L，u = 4.000, P = 0.043；0.001 (0.000~0.003) × 10⁹/L比0.084 (0.038~0.613) × 10⁹/L，u = 0.000，P = 0.006]，至随访或维持治疗7~12个月时仍持续减低[0.157 (0.029~0.428) × 10⁹/L比0.506 (0.414~2.438) × 10⁹/L，u = 1.000，P = 0.018；0.001 (0.000~0.002) × 10⁹/L比0.084 (0.038~0.613) × 10⁹/L，u = 0.000，P = 0.008]。非血液学毒性主要为感染，肺炎最常见，其中3例合并新型冠状病毒肺炎。另外，还可见输注相关反应、肝损害、心血管事件、胃肠道反应等非血液学毒性，均为1~2级，经对症处理后好转。结论：本初步研究提示含奥妥珠单抗方案对FL患者具有潜在疗效，但其安全性特征尤其是感染风险需在更大规模研究中进一步评估。

Abstract: Objective: This study aimed to retrospectively describe the preliminary single-center clinical experience with obinutuzumab-based combination regimens in the treatment of follicular lymphoma (FL) and to analyze the associated treatment efficacy and safety profile. Methods: The efficacy, progression-free survival (PFS), and adverse events in 16 FL patients (12 newly-diagnosed, 4 relapsed/refractory) treated with combination regimens containing Obinutuzumab were analyzed retrospectively. Results: Besides the efficacy could not be evaluated in 1 case who stopped Obinutuzumab due to adverse events, the overall response rate and complete remission rate of the remaining 15 patients who were treated with combined induction regimen containing Obinutuzumab were 86.7% (13/15) and 73.3% (11/15) respectively. At a median follow-up of 27 (8~35) months, PFS at 1 and 2 years were 87.5% and 68.9% respectively. The most common grade 3~4 hematological adverse events were neutropenia. Anemia and thrombocytopenia were mainly grade 1~2. Peripheral blood lymphocyte subsets analysis showed that CD4⁺ T cell count and CD19⁺ B cell count decreased significantly during induction therapy compared with before the treatment [0.181 (0.033~0.628) × 10⁹/L vs. 0.506 (0.414~2.438) × 10⁹/L, u = 4.000, P = 0.043; 0.001(0.000~0.003) × 10⁹/L vs. 0.084 (0.038~0.613) × 10⁹/L, u = 0.000, P = 0.006], and continued to decrease until 7~12 months of follow-up or maintenance therapy [0.157(0.029~0.428) × 10⁹/L vs. 0.506 (0.414~2.438) × 10⁹/L, u = 1.000, P = 0.018; 0.001 (0.000~0.002) × 10⁹/L vs. 0.084 (0.038~0.613) × 10⁹/L, u = 0.000, P = 0.008]. The main nonhematological toxicity was infection, with pneumonia being the most common, including 3 cases with COVID-19. Non-hematological toxicity also included infusion-related reactions, liver damage, cardiovascular events, gastro-intestinal reactions, etc., all of which were grade 1~2, and improved after supportive treatment. Conclusion: This preliminary study suggests that obinutuzumab-based regimens may have potential efficacy in FL patients; however, their safety profile, particularly the risk of infection, requires further evaluation in larger-scale studies.