Sun Yat-Sen University Cancer Center, Guangzhou, China.
Beijing Cancer Hospital, Beijing, China.
J Hematol Oncol. 2021 Feb 15;14(1):25. doi: 10.1186/s13045-020-01020-y.
Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL.
This phase 2 study with Simon's two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification).
In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5-43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29-339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43-106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94-438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab.
In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016.
自然杀伤/T 细胞淋巴瘤（NKTCL）是一种治疗选择有限且预后较差的疾病。单药达雷妥尤单抗在一例单例患者报告中显示出临床活性。我们报告了达雷妥尤单抗治疗复发或难治性（R/R）NKTCL 的 2 期研究的主要分析数据。
这项具有 Simon 两阶段设计的 2 期研究评估了达雷妥尤单抗在组织学证实的结外 NKTCL、鼻型、根据世界卫生组织分类为对≥1 线化疗耐药或复发、不符合其他治疗方式条件的患者中的应用。所有患者接受达雷妥尤单抗 16mg/kg 静脉注射，第 1 和第 2 周期每周 1 次，第 3 至第 6 周期每 2 周 1 次，此后每 4 周 1 次，直至疾病进展或出现无法耐受的毒性；所有周期为 28 天。主要终点是根据修订后的霍奇金和非霍奇金淋巴瘤反应评估标准（卢加诺分类）进行的盲法独立中心评估的客观缓解率（ORR）。
共有 32 名亚洲患者接受了达雷妥尤单抗治疗。ORR 为 25.0%（95%置信区间 [CI]：11.5-43.4）；所有 8 名缓解者均为部分缓解；缓解持续时间的中位数为 55.0 天（95%CI：29-339）。在中位随访 10.2 个月时，中位无进展生存期（PFS）为 53.0 天（95%CI：43-106）；4 个月时的 PFS 率为 13.0%。中位总生存期（OS）为 141.0 天（95%CI：94-438）；6 个月时的 OS 率为 42.9%。19 名（59.4%）患者发生 3/4 级治疗相关不良事件（TEAEs）；最常见的是血小板减少症（25.0%；n=8）。导致死亡的 TEAEs 发生在 4 名患者（死亡、呼吸衰竭、感染性休克和肺炎）；均与达雷妥尤单抗无关。
在复发或难治性 NKTCL 患者中，达雷妥尤单抗单药治疗耐受性良好，无新的安全性问题，缓解率为 25.0%。然而，没有患者达到完全缓解，且缓解持续时间较短。试验注册ClinicalTrials.gov，NCT02927925。2016 年 10 月 7 日注册。
