105例对PD-1通路阻断治疗有反应的默克尔细胞癌患者停止免疫治疗后的疾病进展风险。

Risk of disease progression after discontinuing immunotherapy in 105 patients with Merkel cell carcinoma who responded to PD-1 pathway blockade.

作者信息

Tachiki Lisa, Moshiri Yasman, Hippe Daniel S, Gong Emily, Zawacki Lauren, Pulliam Thomas, Lachance Kristina, Church Candice, Fu Alex, Huynh Emily, Remington Allison J, Harikrishnan Nikhil, Bierma Marika, Doolittle-Amieva Coley, Akaike Tomoko, Park Song Y, Alexander Nora A, Zaba Lisa, Bhatia Shailender, Nghiem Paul T

机构信息

Department of Medicine, Division of Hematology/Oncology, University of Washington, Seattle, Washington, USA

Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.

出版信息

J Immunother Cancer. 2025 Aug 11;13(8):e012123. doi: 10.1136/jitc-2025-012123.

DOI:10.1136/jitc-2025-012123

PMID:40789739

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12352153/

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) are the preferred systemic therapy for most patients with advanced Merkel cell carcinoma (MCC). However, the optimal duration of treatment for patients responding to ICI is unclear. Emerging data from retrospective analyses indicate a higher risk of MCC progression after ICI discontinuation, as compared with continuing ICI.

METHODS

We performed a retrospective cohort study to evaluate the rate of progressive disease (PD) after treatment discontinuation in patients with advanced MCC who experienced objective responses to first-line ICI. We evaluated whether the risk of PD was associated with the reason for treatment discontinuation (elective vs due to toxicity) and depth of response (complete vs partial response (CR vs PR)).

RESULTS

Among 105 responders, 58 discontinued ICI (median treatment duration: 12 months), and 47 continued ICI (median treatment duration: 20 months) at data cut-off. With a median follow-up of 34 months from ICI initiation, 33% of the entire cohort experienced disease progression at 2 years. 2 years after ICI initiation, 39% of patients who discontinued ICI had disease progression, compared with 14% of patients who continued ICI (HR=2.34 (95% CI: 1.07 to 5.12), p=0.034). Among patients who discontinued ICI, those with PR had a numerically higher rate of progression compared with patients with CR at 2 years after ICI discontinuation (56% vs 29%, respectively; HR=1.74 (95% CI: 0.72 to 4.20), p=0.22). Patients who discontinued due to toxicity had numerically higher rates of progression at 2 years (N=28) compared with patients who discontinued electively (N=30) (45% vs 31%, respectively; HR=2.08 (95% CI: 0.79 to 5.46), p=0.14). Among responders who stayed on ICI and had not progressed by 1 year, those who electively discontinued ICI had a high chance of remaining progression-free at 2 years (89%), similar to those who continued ICI (96%, p=0.59).

CONCLUSIONS

This study highlights the high progression risk following ICI discontinuation in advanced MCC, especially among patients with non-CRs or those discontinuing early. While elective discontinuation may be appropriate after durable CRs (response≥1 year), greater caution is warranted in other settings.

摘要

背景

免疫检查点抑制剂（ICI）是大多数晚期默克尔细胞癌（MCC）患者的首选全身治疗方法。然而，对ICI有反应的患者的最佳治疗持续时间尚不清楚。回顾性分析的新数据表明，与继续使用ICI相比，停用ICI后MCC进展的风险更高。

方法

我们进行了一项回顾性队列研究，以评估一线ICI治疗后出现客观反应的晚期MCC患者停药后的疾病进展（PD）率。我们评估了PD风险是否与停药原因（选择性停药与因毒性停药）和反应深度（完全缓解与部分缓解（CR与PR））相关。

结果

在105名有反应的患者中，58名停用了ICI（中位治疗持续时间：12个月），47名继续使用ICI（中位治疗持续时间：20个月）。从ICI开始治疗起，中位随访34个月，整个队列中有33%的患者在2年时出现疾病进展。ICI开始治疗2年后，停用ICI的患者中有39%出现疾病进展，而继续使用ICI的患者中这一比例为14%（HR=2.34（95%CI：1.07至5.12），p=0.034）。在停用ICI的患者中，PR患者在停药2年后的进展率在数值上高于CR患者（分别为56%和29%；HR=1.74（95%CI：0.72至4.20），p=0.22）。因毒性停药的患者在2年时的进展率在数值上高于选择性停药的患者（分别为45%和31%；HR=2.08（95%CI：0.79至5.46），p=0.14）。在继续使用ICI且1年内未进展的有反应患者中，选择性停用ICI的患者在2年时无进展的可能性较高（89%），与继续使用ICI的患者相似（96%，p=0.59）。