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Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Relapsed or Refractory Lymphoma
Felipe Soto1, Ugochi Ebinama2, William P Brasher3
1Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
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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