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Abstract：
Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL.
In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1.
Among 121 treated patients, patients in the auto-HCT-failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT-ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT-failed cohort and 6 months in the auto-HCT-ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT-failed cohort and 1.4 and 5.8 months in the auto-HCT-ineligible cohort respectively. All three patients with complete remission-3% of the auto-HCT-failed cohort-had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification.
Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1.
Among 121 treated patients, patients in the auto-HCT-failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT-ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT-failed cohort and 6 months in the auto-HCT-ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT-failed cohort and 1.4 and 5.8 months in the auto-HCT-ineligible cohort respectively. All three patients with complete remission-3% of the auto-HCT-failed cohort-had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification.
Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
摘要：
复发/难治性弥漫性大B细胞淋巴瘤（DLBCL）患者的治疗选择有限。肿瘤细胞可以利用程序性死亡-1检查点途径来逃避免疫监视。在目前的研究中,我们评估了nivolumab对复发/难治性DLBCL患者程序性死亡-1阻断的疗效和安全性.
在第二阶段,开放标签研究，不适合自体造血细胞移植(auto-HCT)或auto-HCT失败的复发性/难治性DLBCL患者每2周接受一次nivolumab3mg/kg.我们评估了nivolumab的疗效和安全性以及9p24.1的遗传改变。
在121名接受治疗的患者中，auto-HCT失败队列(n=87)中的患者接受的nivolumab剂量中位数为4次,auto-HCT不合格队列中的患者接受的剂量中位数为3次(n=34).自动HCT失败队列的中位随访时间为9个月，自动HCT不合格队列的中位随访时间为6个月，独立评估的客观缓解率分别为10%和3%，中位反应持续时间为11个月和8个月，分别。自动HCT失败队列的中位无进展生存期和总生存期分别为1.9和12.2个月，自动HCT不合格队列的中位无进展生存期和总生存期分别为1.4和5.8个月。所有3名完全缓解的患者-自动HCT失败队列的3％-具有持久的反应（11或更多，14或更多，和17个月）。24%的患者报告了治疗相关的3级和4级不良事件。最常见的是中性粒细胞减少症（4%），血小板减少症(3%),和增加脂肪酶（3％）。在9p24.1分析的所有可评估样品中，16%表现出低水平的拷贝增益,3%具有扩增。
Nivolumab单一疗法与良好的安全性相关，但在不符合auto-HCT或经历auto-HCT失败的DLBCL患者中，总体反应率低。9p24.1的遗传改变在DLBCL中很少见。
在第二阶段,开放标签研究，不适合自体造血细胞移植(auto-HCT)或auto-HCT失败的复发性/难治性DLBCL患者每2周接受一次nivolumab3mg/kg.我们评估了nivolumab的疗效和安全性以及9p24.1的遗传改变。
在121名接受治疗的患者中，auto-HCT失败队列(n=87)中的患者接受的nivolumab剂量中位数为4次,auto-HCT不合格队列中的患者接受的剂量中位数为3次(n=34).自动HCT失败队列的中位随访时间为9个月，自动HCT不合格队列的中位随访时间为6个月，独立评估的客观缓解率分别为10%和3%，中位反应持续时间为11个月和8个月，分别。自动HCT失败队列的中位无进展生存期和总生存期分别为1.9和12.2个月，自动HCT不合格队列的中位无进展生存期和总生存期分别为1.4和5.8个月。所有3名完全缓解的患者-自动HCT失败队列的3％-具有持久的反应（11或更多，14或更多，和17个月）。24%的患者报告了治疗相关的3级和4级不良事件。最常见的是中性粒细胞减少症（4%），血小板减少症(3%),和增加脂肪酶（3％）。在9p24.1分析的所有可评估样品中，16%表现出低水平的拷贝增益,3%具有扩增。
Nivolumab单一疗法与良好的安全性相关，但在不符合auto-HCT或经历auto-HCT失败的DLBCL患者中，总体反应率低。9p24.1的遗传改变在DLBCL中很少见。
