基于抗PD-1抗体的治疗方案在结外NK/T细胞淋巴瘤相关噬血细胞性淋巴组织细胞增生症治疗中的新兴作用。

The emerging role of anti-PD-1 antibody-based regimens in the treatment of extranodal NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis.

作者信息

He Yanxia, Gao Yan, Ping Liqin, He Haixia, Huang Cheng, Bai Bing, Wang Xiaoxiao, Li Zhiming, Cai Qingqing, Huang Yuhua, Pan Xueyi, Zeng Wenbin, Liu Yanan, Huang Huiqiang

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

出版信息

J Cancer Res Clin Oncol. 2023 May;149(5):2017-2027. doi: 10.1007/s00432-022-04147-2. Epub 2022 Jul 9.

DOI:10.1007/s00432-022-04147-2

PMID:35809114

Abstract

PURPOSE

Anti-PD-1 antibody (anti-PD-1 mAb) showed favorable outcomes in some patients with relapsed/refractory (r/r) extranodal NK/T-cell lymphoma (ENKTL). However, the role of anti-PD-1 antibody in NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (NK/T-LAHS) remains unclear. Here, we evaluated the efficacy and toxicity of anti-PD-1 antibody-based treatment in NK/T-LAHS patients.

METHODS

The clinical data of 98 patients diagnosed with NK/T-LAHS at Sun Yat-sen University Cancer Center and the First Affiliated Hospital of Guangdong Pharmaceutical University from May 2014 to November 2021 were retrospectively analyzed. All patients received anti-HLH [HLH-2004 (etoposide, dexamethasone, cyclosporine A) or DEP-based (liposomal doxorubicin, etoposide, methylprednisolone)] regimen and sequential anti-ENKTL chemotherapy (ChT) combined with anti-PD-1 antibody or not.

RESULTS

The overall response rate (ORR) of the anti-PD-1 mAb plus ChT regimens was higher than that of the ChT regimens (73.3% vs. 45.5%, P = 0.041). The toxicity of the anti-PD-1 mAb plus ChT regimens was tolerable. Except for higher rate of neutropenia, no significant difference in adverse events (AEs) was observed between the two groups. When the optimal response to anti-ENKTL was achieved, the median EBV DNA levels in patients who received anti-PD-1 mAb plus ChT were significantly lower than patients who received ChT only (878 copies/mL vs. 18,600 copies/mL, P = 0.001). With a median follow-up of 26.6 months (range 0-65.9 months), the median overall survival (mOS) was 3.5 months (95% CI：2.3-4.7 months). Patients treated with anti-PD-1 mAb plus ChT experienced a longer mOS than those who received ChT only [5.2 months (95% CI: 2.5-7.8 months) vs. 1.5 months (95% CI: 0.5-2.6 months), P = 0.002]. Cox multivariate analysis found that anti-PD-1 mAb was an independent prognostic factor for all NK/T-LAHS patients.

CONCLUSION

In conclusion, anti-PD-1 mAb combined with ChT regimens seemed to be associated with prolonged survival in NK/T-LAHS patients and may represent a potentially promising treatment strategy for this population.

摘要

目的

抗程序性死亡蛋白 1 抗体（抗 PD-1 单克隆抗体）在部分复发/难治性（r/r）结外 NK/T 细胞淋巴瘤（ENKTL）患者中显示出良好疗效。然而，抗 PD-1 抗体在 NK/T 细胞淋巴瘤相关噬血细胞性淋巴组织细胞增生症（NK/T-LAHS）中的作用仍不明确。在此，我们评估了基于抗 PD-1 抗体的治疗对 NK/T-LAHS 患者的疗效和毒性。

方法

回顾性分析 2014 年 5 月至 2021 年 11 月在中山大学肿瘤防治中心和广东药科大学附属第一医院诊断为 NK/T-LAHS 的 98 例患者的临床资料。所有患者均接受抗噬血细胞性淋巴组织细胞增生症方案[HLH-2004（依托泊苷、地塞米松、环孢素 A）或基于 DEP 的方案（脂质体阿霉素、依托泊苷、甲泼尼龙）]以及序贯抗 ENKTL 化疗（ChT），部分患者联合抗 PD-1 抗体。

结果

抗 PD-1 单克隆抗体联合 ChT 方案的总缓解率（ORR）高于单纯 ChT 方案（73.3% 对 45.5%，P = 0.041）。抗 PD-1 单克隆抗体联合 ChT 方案的毒性可耐受。除中性粒细胞减少发生率较高外，两组不良事件（AE）无显著差异。当达到对抗 ENKTL 的最佳缓解时，接受抗 PD-1 单克隆抗体联合 ChT 的患者的 EBV DNA 水平中位数显著低于仅接受 ChT 的患者（878 拷贝/mL 对 18,600 拷贝/mL，P = 0.001）。中位随访 26.6 个月（范围 0 - 65.9 个月），中位总生存期（mOS）为 3.5 个月（95%CI：2.3 - 4.7 个月）。接受抗 PD-1 单克隆抗体联合 ChT 治疗的患者的 mOS 长于仅接受 ChT 的患者[5.2 个月（95%CI：2.5 - 7.8 个月）对 1.5 个月（95%CI：0.5 - 2.6 个月），P = 0.002]。Cox 多因素分析发现抗 PD-1 单克隆抗体是所有 NK/T-LAHS 患者的独立预后因素。