Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Relapsed or Refractory Lymphoma.

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia Pub Date : 2025-05-16 DOI:10.1016/j.clml.2025.05.008

Felipe Soto, Ugochi Ebinama, William P Brasher, William C Harding, Alberto Goizueta, Jeremy R Walder, Alexandra Ewing, Vickie R Shannon, Saadia A Faiz, Mehmet Altan, Girish Shroff, Lei Feng, Sattva Neelapu, Sairah Ahmed, Loretta J Nastoupil, Ajay Sheshadri

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引用次数: 0

Abstract

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized relapsed/refractory lymphoma treatment but can cause severe immune-related adverse events (irAEs), including pneumonitis. The incidence and risk factors for ICI-pneumonitis in real-world lymphoma cohorts remain unreported.

Methods: We retrospectively reviewed 302 lymphoma patients treated with PD-1 inhibitors at MD Anderson (2015-2022). A multidisciplinary team adjudicated grade ≥ 2 pneumonitis (CTCAEv5). We analyzed demographic, clinical, and treatment data. Cox proportional hazards models assessed univariate and multivariate associations (P < .1 for inclusion).

Results: Pneumonitis occurred in 16/302 patients (5%). Univariate analysis identified risk factors: CTLA-4 combination (13.5, 95% CI, 1.7-104.7, P = .01), pre-ICI hypoxemia (HR = 9.2, 95% CI, 2.9-29, P < .001), pre-ICI dyspnea (HR = 3.1, 95% CI, 1.1-8.6, P = .02), CD25-ADC (HR = 4.6, 95% CI, 1.04-21.03, P = .04), and IAP antagonists (HR = 9.2, 95% CI, 1.18-71.2, P = .03). In multivariate analysis, independent risk factors included pre-ICI dyspnea (HR = 4.6, 95% CI, 1.5-14, P = .007), CTLA-4 combination (HR = 24, 95% CI, 2.9-204, P = .003), IAP antagonists (HR = 23.8, 95% CI, 2.6-218, P = .005), and PI3K inhibitors (HR = 14.6, 95% CI, 1.7-123, P = .01). Pneumonitis was not associated with mortality (HR = 0.7, 95% CI, 0.2-2.5, P = .69).

Discussion: ICI-pneumonitis incidence was 5%, typically low-grade. CD25-ADC's link to pneumonitis may stem from regulatory T cell depletion. IAP antagonists, which enhance Th1/TNF-α responses, may result in cytotoxic pulmonary injury. PI3K inhibitors, which have been independently associated with pneumonitis, may synergize with ICIs to potentiate risk for pneumonitis.

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复发或难治性淋巴瘤中与检查点抑制剂相关的肺炎的发病率和危险因素

免疫检查点抑制剂（ICI）已经彻底改变了复发/难治性淋巴瘤的治疗，但可能导致严重的免疫相关不良事件（irAEs），包括肺炎。真实世界淋巴瘤队列中ci -肺炎的发病率和危险因素仍未报道。方法：我们回顾性分析了MD安德森（2015-2022）接受PD-1抑制剂治疗的302例淋巴瘤患者。多学科团队判定≥2级肺炎（CTCAEv5）。我们分析了人口统计、临床和治疗数据。Cox比例风险模型评估了单因素和多因素相关性（纳入时P < 0.1）。结果：302例患者中16例（5%）发生肺炎。单因素分析确定了危险因素：CTLA-4联合（13.5,95% CI, 1.7-104.7, P = 0.01）、ici前低氧血症（HR = 9.2, 95% CI, 2.9-29, P < 0.01）、ici前呼吸困难（HR = 3.1, 95% CI, 1.1-8.6, P = 0.02）、CD25-ADC （HR = 4.6, 95% CI, 1.04-21.03, P = 0.04）和IAP拮抗剂（HR = 9.2, 95% CI, 1.18-71.2, P = 0.03）。在多因素分析中，独立危险因素包括ici前呼吸困难（HR = 4.6, 95% CI, 1.5-14, P = .007）、CTLA-4联合（HR = 24, 95% CI, 2.9-204, P = .003）、IAP拮抗剂（HR = 23.8, 95% CI, 2.6-218, P = .005）和PI3K抑制剂（HR = 14.6, 95% CI, 1.7-123, P = .01）。肺炎与死亡率无关（HR = 0.7, 95% CI, 0.2-2.5, P = 0.69）。讨论：ci -肺炎发生率为5%，典型的低级别。CD25-ADC与肺炎的联系可能源于调节性T细胞耗竭。IAP拮抗剂可增强Th1/TNF-α反应，可能导致细胞毒性肺损伤。与肺炎独立相关的PI3K抑制剂可能与ICIs协同作用，增加肺炎的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Lymphoma, Myeloma & Leukemia ONCOLOGY-HEMATOLOGY

CiteScore

2.70

自引率

3.70%

发文量

1606

审稿时长

26 days

期刊介绍： Clinical Lymphoma, Myeloma & Leukemia is a peer-reviewed monthly journal that publishes original articles describing various aspects of clinical and translational research of lymphoma, myeloma and leukemia. Clinical Lymphoma, Myeloma & Leukemia is devoted to articles on detection, diagnosis, prevention, and treatment of lymphoma, myeloma, leukemia and related disorders including macroglobulinemia, amyloidosis, and plasma-cell dyscrasias. The main emphasis is on recent scientific developments in all areas related to lymphoma, myeloma and leukemia. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.