Late-onset Pleural and Pericardial Effusion as Immune-related Adverse Events after 94 Cycles of Nivolumab

Sawada, Renshi; Uchino, Junichi; Okura, Naoko; Morimoto, Yoshie; Iwasaku, Masahiro; Kaneko, Yoshiko; Takayama, K.

doi:10.2169/internalmedicine.7219-21

Cited by 8 publications

(7 citation statements)

References 16 publications

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“…developed pleural effusion after applying ICIs and using chemotherapy, respectively; ICIs significantly increased the risk of pleural effusion compared with chemotherapy (P < 0.05). Pleural effusion has been reported as an irAE, but there are few studies on ICIs-related pleural effusion, most of which are case reports (93)(94)(95). Two patients were reported to develop recurrent pleural effusions that accumulated rapidly within days after each puncture and required multiple thoracentesis for the first 8 weeks after administration of nivolumab (95).…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials

Liu

Luo²,

Jie³

et al. 2023

Front. Immunol.

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BackgroundIn recent years, immune checkpoint inhibitors (ICIs) had extremely rapid growth in anti-cancer and improved outcomes of many malignancies, specifically lung cancer. However, the incidence of ICIs-related adverse events also raised. Using this meta-analysis, ICIs-related respiratory disorders were investigated in lung cancer patients.MethodsUsing Cochrane Library, Embase, and PubMed databases, we performed an integrated search for randomized controlled trials (RCTs) to compare respiratory disorders among different regimens. The data was prepared with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline, and the quality of included studies was evaluated based on the Cochrane manual.ResultsIn total, 22 RCTs were involved in this meta-analysis. Compared with ICIs, chemotherapy reduced the risk of interstitial lung disease (p = 0.03; SMD: 2.81; 95% CI: 1.08, 7.27), pleural effusion (p = 0.002; SMD: 2.12; 95% CI: 1.32, 3.42), and pneumonitis (p < 0.00001; SMD: 9.23; 95% CI: 4.57, 18.64). ICIs plus chemotherapy could provide a higher probability for patients to suffer pneumonitis than chemotherapy (p = 0.01; SMD: 1.96; 95% CI: 1.17, 3.28). In addition, single ICI brought a lower likelihood for patients suffering pneumonitis than double ICIs (p = 0.004; SMD: 2.17; 95% CI: 1.27, 3.69).ConclusionICIs-based treatment, such as ICIs alone, ICIs plus chemotherapy and double ICIs, can raise the incidences of some respiratory disorders in patients with lung cancer. It suggests that ICIs should be conducted based on a comprehensive consideration to prevent ICIs-related respiratory disorders. To a certain degree, this study might be provided to the clinician as a reference for ICIs practice.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022378901, identifier (CRD42022378901).

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Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials

Liu

Luo²,

Jie³

et al. 2023

Front. Immunol.

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“…As shown in Table 1, these publications reported a total of 21 cases [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] (7 women; 14 men) of patients with an age range between 46 and 79 years and with a median of 65 years. The most frequent histology was lung adenocarcinoma (n = 15), followed by squamous cell carcinoma of the lung (n = 3).…”

Section: Discussionmentioning

confidence: 99%

“…The pericardial effusion occurred in different cycles, with a range between 1 and 94. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] In most cases (76%) pericardiocentesis was performed due to severe pericardial effusion, two of them required admission to the intensive care unit (ICU) requiring intubation and invasive mechanical ventilation for 2-4 days. 25,26 Only 48% received treatment with corticosteroid therapy.…”

Section: Discussionmentioning

confidence: 99%

Pericardial effusion with pembrolizumab

Madrigal

Pérez

Garcés

et al. 2022

J Oncol Pharm Pract

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Introduction The treatment of non-small cell lung cancer (NSCLC) has profoundly changed on account of the arrival of new therapies, like immunotherapy. Within this group of drugs, those aimed at the programmed cell death-1 or programmed cell death ligand-1(PD1/PDL-1) are very relevant, for example, Pembrolizumab. Although its adverse reactions are generally mild and well tolerated, it has been associated with certain immune-related adverse events (IrAEs) than can be serious and affect any organ. Case report A 62-year-old woman diagnosed with stage IV NSCLC with a single bone metastasis and PD-L1 expression of 60% started treatment with cisplatin-pemetrexed-pembrolizumab, and maintenance with pembrolizumab. Management and outcome The patient attended the ER with pericardial effusion that was assumed to be a Pembrolizumab IrAE and was managed with corticosteroids. The patient fully recovered but immunotherapy was not reintroduced due to the severity of the AE. Discussion The cardiovascular system is among the least affected organs by immunotoxicity, with an incidence between 0.09–0.6%. However, some authors suspect the incidence is underestimated. Median time to onset is highly variable, ranging from 6 weeks since the first dose to 2 years after discontinuation of the treatment. There are not guidelines on the most effective management of the IrAEs, but according to the pharmaceutical reference, corticosteroids should be initiated followed by a progressive reduction. If no response is obtained, another immunosuppressive agent should be added. The determination to restart immunotherapy depends on the severity of the adverse reaction, the availability of other alternative treatments, and the cancer response.

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“…The onset of irSerositis is often acute with respiratory failure and chest pain [ 13 – 16 ], but can also be slowly progressive with weight gain or progressive exertional dyspnea (Case 1–4 [ 7 ]). Symptom onset after initiation of immunotherapy ranged from 8 to 52 weeks but earlier and later onset ranging from seven days [ 17 ] to 72 weeks [ 18 ] or even as late as 200 weeks after start of checkpoint therapy [ 19 ] has been reported. Diagnosis may be difficult since progression of disease with malignant infiltrates has to be distinguished from immune-mediated effusions and can appear simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Checkpoint-inhibitor induced Polyserositis with Edema

Zierold

Akcetin

Gresser

et al. 2022

Cancer Immunol Immunother

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Background As immune checkpoint inhibitors (ICI) are increasingly being used due to effectiveness in various tumor entities, rare side effects occur more frequently. Pericardial effusion has been reported in patients with advanced non-small cell lung cancer (NSCLC) after or under treatment with immune checkpoint inhibitors. However, knowledge about serositis and edemas induced by checkpoint inhibitors in other tumor entities is scarce. Methods and results Four cases with sudden onset of checkpoint inhibitor induced serositis (irSerositis) are presented including one patient with metastatic cervical cancer, two with metastatic melanoma and one with non-small cell lung cancer (NSCLC). In all cases treatment with steroids was successful in the beginning, but did not lead to complete recovery of the patients. All patients required multiple punctures. Three of the patients presented with additional peripheral edema; in one patient only the lower extremities were affected, whereas the entire body, even face and eyelids were involved in the other patients. In all patients serositis was accompanied by other immune-related adverse events (irAEs). Conclusion ICI-induced serositis and effusions are complex to diagnose and treat and might be underdiagnosed. For differentiation from malignant serositis pathology of the punctured fluid can be helpful (lymphocytes vs. malignant cells). Identifying irSerositis as early as possible is essential since steroids can improve symptoms.

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Late-onset Pleural and Pericardial Effusion as Immune-related Adverse Events after 94 Cycles of Nivolumab

Cited by 8 publications

References 16 publications

Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials

Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials

Pericardial effusion with pembrolizumab

Checkpoint-inhibitor induced Polyserositis with Edema

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