1 Mayo Clinic, Rochester, MN.
2 University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands, on behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC.
J Clin Oncol. 2019 Feb 20;37(6):481-489. doi: 10.1200/JCO.18.00766. Epub 2019 Jan 8.
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.
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 检查点途径逃避免疫监视。在本研究中，我们评估了纳武单抗对复发/难治性 DLBCL 患者的疗效和安全性。
在这项 II 期、开放标签研究中，不适合自体造血细胞移植（auto-HCT）或自体 HCT 失败的复发/难治性 DLBCL 患者接受纳武单抗 3 mg/kg，每 2 周一次。我们评估了纳武单抗的疗效和安全性，以及 9p24.1 的基因改变。
在 121 例接受治疗的患者中，自体 HCT 失败队列（n = 87）患者接受了中位数为 4 次纳武单抗剂量，自体 HCT 不适用队列（n = 34）患者接受了中位数为 3 次剂量。在自体 HCT 失败队列的中位随访 9 个月和自体 HCT 不适用队列的中位随访 6 个月时，独立评估的客观缓解率分别为 10%和 3%，中位缓解持续时间分别为 11 个月和 8 个月。自体 HCT 失败队列的中位无进展生存期和总生存期分别为 1.9 个月和 12.2 个月，自体 HCT 不适用队列分别为 1.4 个月和 5.8 个月。完全缓解-3%的自体 HCT 失败队列中的 3 例患者均有持久缓解（11 个月以上、14 个月以上和 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%）和脂肪酶升高（3%）。所有可评估 9p24.1 分析的样本中，16%表现为低水平拷贝数增加，3%表现为扩增。
纳武单抗单药治疗在不适合自体 HCT 或自体 HCT 失败的 DLBCL 患者中具有良好的安全性，但总体反应率较低。9p24.1 的基因改变在 DLBCL 中很少见。
