Severe immune-related hyperthermia followed by immune-related pneumonitis with PD-1 inhibitor (sintilimab) in small cell lung cancer: A case report.
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SUBMITTER: Li YH
PROVIDER: S-EPMC8169295 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundImmune-related pneumonitis is a rare and potentially fatal adverse event associated with sintilimab. We aimed to develop and validate a nomogram for predicting the risk of immune-related pneumonitis in patients treated with sintilimab.MethodsThe least absolute shrinkage and selection operator (LASSO) regression was used to determine risk factors. Multivariable logistic regression was used to establish a prediction model. Its clinical validity was evaluated using calibration, discrimination, decision, and clinical impact curves. Internal validation was performed against the validation set and complete dataset.ResultsThe study included 632 patients; 59 were diagnosed with immune-related pneumonitis. LASSO regression analysis identified that the risk factors for immune-related pneumonitis were pulmonary metastases (odds ratio [OR], 4.015; 95% confidence interval [CI]: 1.725-9.340) and metastases at >3 sites (OR, 2.687; 95% CI: 1.151-6.269). The use of combined antibiotics (OR, 0.247; 95% CI: 0.083-0.738) and proton pump inhibitors (OR, 0.420; 95% CI: 0.211-0.837) were protective factors. The decision and clinical impact curves showed that the nomogram had clinical value for patients treated with sintilimab.ConclusionsWe have developed and validated a practical nomogram model of sintilimab-associated immune-related pneumonitis, which provides clinical value for determining the risk of immune-related pneumonitis and facilitating the safe administration of sintilimab therapy.
| S-EPMC10905226 | biostudies-literature
Project description:BackgroundCombination therapy with immune checkpoint inhibitors (ICIs) and antiangiogenic agents is generally effective and well tolerated and might be effective for metastatic urothelial carcinoma (UC). However, ICI treatment is often associated with unique responses, such as pseudoprogression and ICI-related pneumonitis (CIP), which may influence clinical decision making and affect treatment. Although there have been many studies on the mechanism of pseudoprogression and CIP, the characteristics and relationship of these special events in a clinical setting remain rarely reported.Case presentationHere, we present a patient with lung metastatic UC who underwent surgery and two lines of chemotherapy. The programmed cell death-1 (PD-1) inhibitor nivolumab and antiangiogenics agent bevacizumab were used as maintenance treatments. The patient experienced pseudoprogression after 2 PD-1 inhibitor cycles. The lesions in both lungs were enlarged on computed tomography (CT) imaging, and treatments were continued for another two cycles, after which the tumor size decreased to below baseline, followed by a durable response. However, after 4 months of pseudoprogression, the patient then developed CIP. The CIP was responsive to glucocorticoid therapy but recurred during ICI rechallenge, leading to the termination of immune therapy. Ultimately, the patient achieved durable, stable disease for over 18 months without further anticancer treatment.ConclusionsOur case shows that pseudoprogression can occur in UC during immunotherapy even when combined with an effective antiangiogenic agent. In addition, pseudoprogression may be correlated with future adverse effects and a durable response. In the management of CIP, early rechallenge with ICIs may lead to CIP recurrence, which could be more severe and needs to be treated early and with appropriate drugs. Clinicians should be aware of atypical responses to ICIs and adjust the treatment plan accordingly.
| S-EPMC7884808 | biostudies-literature
Project description:PurposeWhilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer.Methods and materialsFrom January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables.ResultsWith a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (P=0.05), mean lung dose (MLD, P=0.038), percent volume of lung receiving ≥5 Gy (V5, P=0.012) and percent volume of lung receiving ≥20 Gy (V20, P=0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, P=0.004).ConclusionsTreatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice.
| S-EPMC9251068 | biostudies-literature
Project description:BACKGROUND:Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4-6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lung cancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ?12 weeks of immunosuppression. METHODS:Patients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ?12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&E staining and multiplex immunofluorescence (mIF), where available. RESULTS:Among 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0-50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3-12 weeks), with all patients requiring steroid reintroduction when tapered to ?10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16-43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper. CONCLUSIONS:A subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ?12 weeks, and has distinct clinicopathological features.
| S-EPMC7304886 | biostudies-literature
Project description:PurposeInvestigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients.Experimental designAmong patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis.ResultsAmong 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, and 4 lung cancer) developed pneumonitis. Five patients received nivolumab monotherapy, and 15 received combination therapy. The median time from therapy initiation to pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The AIP/ARDS pattern had the highest grade, followed by COP, whereas NSIP and HP had lower grade (median grade: 3, 2, 1, 1, respectively; P = 0.006). The COP pattern was most common in all tumors and treatment regimens. Most patients (17/20; 85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; 2 of them developed recurrent pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment.ConclusionsPD-1 inhibitor-related pneumonitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent pneumonitis and pneumonitis flare were noted in a few patients. Clin Cancer Res; 22(24); 6051-60. ©2016 AACRSee related commentary by Castanon, p. 5956.
| S-EPMC5161686 | biostudies-literature
Project description:ObjectivesThis study aimed at establishing a mouse model of immune-related adverse in humanized BALB/c-hPD1/hCTLA4 mice to investigate their potential pathogenesis and explore therapeutic targets for immune-related arthritis and pneumonitis.MethodsHumanized BALB/c-hPD1/hCTLA4 mice were injected with vehicle or collagen-specific antibodies (CA) and immune checkpoint inhibitors (ICI, ipilimumab, anti-human CTLA-4; and nivolumab, anti-human PD-1), and some mice were treated with anti-TNF-α antibody, leading to the control, collagen antibody-induced arthritis (CAIA), CAIA+ICI and treatment groups. The severity of clinical arthritis and pneumonitis in mice was monitored longitudinally and the pathological changes in the joints and lungs were histologically analyzed and the contents of lung hydroxyproline were measured. The frequency of different subsets of T cells was analyzed by flow cytometry and multiplex immunofluorescency.ResultsCompared with the control, the ICI group of mice developed the delayed onset of moderate degrees of arthritis while the CAIA+ICI group of mice exhibited the early onset of severe arthritis. Treatment with ICI caused severe pneumonitis, especially in the mice with CA. Flow cytometry analysis indicated a significantly higher frequency of splenic TNF-α+CD4+ and TNF-α+CD8+ T cells, but not other subsets of T cells tested, in the CAIA+ICI group of mice, relative to that in other groups of mice. Treatment with anti-TNF-α significantly mitigated the severity of arthritis and pneumonitis as well as deposition of collagen in lung of mice. The treatment also decreased the frequency of TNF-α+CD4+ and TNF-α+CD8+ T cells as well as effector memory T cells in the periphery lymph orangs and lungs of mice.ConclusionsWe successfully established a humanized mouse model of ICI-related severe arthritis and pneumonitis with a higher frequency of TNF-α+ T cells, which were significantly mitigated by anti-TNF-α treatment. Conceptually, ICI treatment can induce multiple autoimmune-like diseases in autoimmune-prone individuals and TNF-α+ T cells may be therapeutic targets for intervention of immune-related arthritis and pneumonitis.
| S-EPMC9396351 | biostudies-literature
Project description:PurposeImmune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis.Materials and methodsIn this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated.ResultsPneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031).ConclusionSequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.
| S-EPMC7812016 | biostudies-literature
Project description:The main cause of acute kidney injury in patients receiving immune checkpoint inhibitors (ICIs) is acute interstitial nephritis. However, as their use continues to increase, other kidney manifestations are being described. We report 3 cases of patients treated with ICIs who developed predominantly electrolyte disorders secondary to renal tubular acidosis as an immune-related adverse event and discuss the potential mechanism. Nongap acidosis in combination with hypokalemia should raise suspicion for distal renal tubular acidosis in patients treated with ICIs.
| S-EPMC7568062 | biostudies-literature
Project description:We conducted single-cell and T-cell receptor transcriptomic sequencing on the bronchoalveolar lavage fluid from five patients with grade ≥2 immune checkpoint inhibitor-related pneumonitis. Our analyses revealed a prominent enrichment of T cells in the bronchoalveolar lavage fluid of patients with immune checkpoint inhibitor-related pneumonitis.
2024-09-13 | GSE277136 | GEO
Project description:Neoadjuvant PD-(L)1 inhibitors may be promising for locally advanced non-small cell lung cancer (NSCLC) with potential pathological and survival benefits. But severe immune-related adverse events (irAEs) may cause fatal consequences which require early identification and timely intervention. The basis for most of these adverse events is a reactive hyperactivated T-cell response to normal tissues that results in the production of high levels of CD4 T-helper cell cytokines or increased migration of cytolytic CD8 T cells in normal tissues. It is recommended that all patients receiving PD-(L)1 inhibitors routinely have thyroid function studies, complete blood counts, and liver function and metabolic panels at each treatment and at intervals of 6 to 12 weeks for the first 6 months after finishing treatment. Herein, we report a rare case who had two grade 3-4 irAEs consecutively occurring after PD-1 induction therapy and surgery. A 59-year-old man with stage IIIA squamous cell lung cancer receiving 3 cycles of neoadjuvant nab-paclitaxel, carboplatin, and nivolumab was reevaluated for resectability. The patient experienced acute serum transaminase elevation right after induction therapy. Seven days after surgery he had severe pneumonia. These two serious complications were both eventually relieved by a month long treatment of corticosteroids but not regular medicine which verified the diagnosis of irAEs. Although results of clinical trials of neoadjuvant immunotherapy are worth expecting, our case calls attention to careful surveillance and timely management of irAEs during the perioperative use of PD-(L)1 inhibitors. We also further discuss the standard use of corticosteroids for irAEs based on a review of literature.
| S-EPMC8435383 | biostudies-literature