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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Cox proportional hazards models assessed univariate and multivariate associations (P < .1 for inclusion).</p><p><strong>Results: </strong>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).</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Relapsed or Refractory Lymphoma.\",\"authors\":\"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\",\"doi\":\"10.1016/j.clml.2025.05.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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).</p><p><strong>Discussion: </strong>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.</p>\",\"PeriodicalId\":10348,\"journal\":{\"name\":\"Clinical Lymphoma, Myeloma & Leukemia\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Lymphoma, Myeloma & Leukemia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.clml.2025.05.008\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Lymphoma, Myeloma & Leukemia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.clml.2025.05.008","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
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。
Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Relapsed or Refractory Lymphoma.
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.
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.
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