Refractory constrictive pericarditis caused by an immune checkpoint inhibitor properly managed with infliximab: a case report

Abstract Background Immune checkpoint inhibitors (ICIs) can cause cardiac immune-related adverse events (irAEs), including pericarditis. Cardiovascular events related to pericardial irAE are less frequent, but fulminant forms can be fatal. However, the diagnosis and treatment strategies for pericardial irAE have not established. Case summary A 58-year-old man was diagnosed with advanced non-small-cell lung cancer and nivolumab was administered as 5th-line therapy. Eighteen months after the initiation of nivolumab, the patient developed limb oedema and increased body weight. Although a favourable response of the cancer was observed, pericardial thickening and effusion were newly detected. He was diagnosed with irAE pericarditis after excluding other causes of pericarditis. Nivolumab was suspended and a high-dose corticosteroid was initiated. However, right heart failure (RHF) symptoms were exacerbated during the tapering of corticosteroid because acute pericarditis developed to steroid-refractory constrictive pericarditis. To suppress sustained inflammation of the pericardium, infliximab, a tumour necrosis factor-alfa inhibitor, was initiated. After the initiation of infliximab, the corticosteroid dose was tapered without deterioration of RHF. Exacerbation of lung cancer by irAE treatment including infliximab was not observed. Discussion IrAE should be considered when pericarditis develops after the administration of ICI even after a long period from its initiation. Infliximab rescue therapy may be considered as a 2nd-line therapy for steroid-refractory irAE pericarditis even with constrictive physiology.

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Immune-related intestinal pseudo-obstruction associated with nivolumab treatment in a lung cancer patient

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217738325 ◽

2017 ◽

Vol 25 (2) ◽

pp. 487-491 ◽

Cited By ~ 10

Author(s):

Georgios Fragulidis ◽

Eirini Pantiora ◽

Vasiliki Michalaki ◽

Elissaios Kontis ◽

Elias Primetis ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Effects ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

High Dose ◽

Checkpoint Inhibition ◽

Immune Checkpoint Inhibition ◽

Gradual Improvement ◽

Organ Systems

Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a new therapeutic approach with significant survival benefit for patients with several cancer types. However, their use can be associated with unique immune-related adverse effects as a consequence of impaired self-tolerance due to loss of T-cell inhibition via a nonselective activation of the immune system. Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy with remarkable responses in nonsmall cell lung cancer patients. We present a 62-year-old Caucasian male with recurrent lung adenocarcinoma and currently under third-line therapy with nivolumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After four days of conservative treatment, the patient underwent exploratory laparotomy where no cause of ileus was discovered. Postoperative the ileus persisted and considering that an adverse effect of the immune checkpoint inhibition therapy occurred, the patient received high-dose prednisone resulting in gradual improvement of symptoms. Immune checkpoint inhibitors may induce adverse effects to unaffected organ systems and tissues including the skin, gastrointestinal, hepatic, pulmonary, and endocrine system. The mainstay treatment consists of immunosuppression with corticosteroids in the majority of cases. As the clinical use of immune checkpoint inhibitors is expanding rapidly, there is an emergence of unique immune-related adverse effects in a growing patient population. Gaining early awareness is essential in these patients in order to ensure prompt diagnosis and management.

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Body mass index in non-small cell lung cancer patients treated with anti-PD-1 immune checkpoint inhibitors.

Journal of Global Oncology ◽

10.1200/jgo.2019.5.suppl.68 ◽

2019 ◽

Vol 5 (suppl) ◽

pp. 68-68

Author(s):

Akiko Tateishi ◽

Hidehito Horinouchi ◽

Ken Masuda ◽

Hitomi Jo ◽

Yuki Shinno ◽

...

Keyword(s):

Lung Cancer ◽

Body Mass Index ◽

Small Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

Line Therapy ◽

Nsclc Patients

68 Background: Previous retrospective analyses have revealed higher response rates and a trend towards longer progression-free survival (PFS) and overall survival (OS) in response to immune checkpoint inhibitors (ICIs) in overweight patients. There are few reports concerning the association between the overweight state and the efficacy of ICIs specifically in non-small cell lung cancer (NSCLC) patients. We investigated the association between the body mass index (BMI) and the efficacy of ICIs in patients with NSCLC. Methods: Patients with advanced NSCLC who received ICI therapy (nivolumab or pembrolizumab) at the National Cancer Center Hospital from January 2016 to December 2018 were included in this retrospective cohort study. Based on their BMI, the patients were categorized into the overweight (A) group (BMI ≥25) and the non-overweight (B) group (BMI < 25). The PFS was compared between the two groups as the primary outcome. Results: Data of a total of 323 patients (median age, 63 years) were analyzed; 87 (26.9%)/43 (13.3%)/193 (59.8%) patients received pembrolizumab as 1st line therapy, pembrolizumab as 2nd line therapy, and nivolumab, respectively. Tumor proportion score was ≥50% in 58.4% (139/238) patients. The ECOG-PS was ≥2 in 37 patients (11.5%). The median body weight was 58.1, and the median BMI was 21.4. Of the 323 patients, 46 (14.2%) were categorized into group A (overweight) and 277 (85.8%) into group B (non-overweight). The median PFS and OS in two groups were as follows: A, 6.9 m/B, 5.6 m (HR 0.84, 95% CI [0.57-1.25], p = 0.38), and A, 22.3 m/B, 15.4 m (HR 0.90, 95% CI [0.56-1.43], p = 0.64), respectively. In accordance with the ICI regimen that the patients received, the PFS was A, 7.9 m/B, 7.8 m (HR 0.86, 95%CI [0.37-2.04], p = 0.74) in the patients who received pembrolizumab as 1st line therapy, A, 7.5 m/B, 5.3 m (HR 0.60, 95% CI [0.18-2.00], p = 0.40) in the patients who received pembrolizumab as 2nd line therapy, and A, 6.5 m/B, 4.4 m (HR 0.84, 95% CI [0.52-1.36], p = 0.48) in the patients who received nivolumab. Conclusions: Overweight NSCLC patients treated with ICIs showed a trend (non-statistically significant) towards a longer PFS as compared to non-overweight patients.

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Immune checkpoint inhibitors in first-line therapy of advanced non-small cell lung cancer

Current Opinion in Oncology ◽

10.1097/cco.0000000000000351 ◽

2017 ◽

Vol 29 (2) ◽

pp. 97-104 ◽

Cited By ~ 19

Author(s):

Jordi Remon ◽

Benjamin Besse

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

First Line Therapy ◽

Line Therapy

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Resistance to immune checkpoint inhibitors in non-small cell lung cancer: biomarkers and therapeutic strategies

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920937902 ◽

2020 ◽

Vol 12 ◽

pp. 175883592093790 ◽

Cited By ~ 1

Author(s):

Robert J. Walsh ◽

Ross A. Soo

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Treatment Strategies ◽

Small Cell ◽

Small Cell Lung ◽

Secondary Resistance

The treatment landscape for patients with advanced non-small cell lung cancer has evolved greatly with the advent of immune checkpoint inhibitors. However, many patients do not derive benefit from checkpoint blockade, developing either primary or secondary resistance, highlighting a need for alternative approaches to modulate immune function. In this review, we highlight the absence of a common definition of primary and secondary resistance and summarize their frequency and clinical characteristics. Furthermore, we provide an overview of the biomarkers and mechanisms of resistance involving the tumor, the tumor microenvironment and the host, and suggest treatment strategies to overcome these mechanisms and improve clinical outcomes.

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Role of immunotherapy in oligometastatic nonsmall cell lung cancer

BMJ Case Reports ◽

10.1136/bcr-2020-241070 ◽

2021 ◽

Vol 14 (5) ◽

pp. e241070

Author(s):

Yehuda Galili ◽

Ahmad El-Far ◽

Jennifer Tseng ◽

Steve Carlan

Keyword(s):

Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Treatment Strategies ◽

Nonsmall Cell Lung Cancer ◽

Current Treatment ◽

Adjunctive Treatment ◽

Comfort Care ◽

Metastatic Lung

The approach to metastatic lung cancer has long been focused on palliation therapy and comfort care. Recently, significant subsets of patients who suffer from a limited form of the disease have shown curative outcomes. The oligometastatic disease theory was first introduced in 1995, and since has been applied to many solid tumours. In oligometastatic nonsmall cell lung cancer, current treatment strategies include surgery, radiation therapy and chemotherapy. There is evidence of astounding survival benefits in selected patients treated with immune checkpoint inhibitors. We present three cases with oligometastatic nonsmall cell lung cancer treated with pembrolizumab, an immune checkpoint inhibitor, and describe the outcomes. Immunotherapy with pembrolizumab appears to be an effective adjunctive treatment with low toxicity in oligometastatic nonsmall cell lung cancer.

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Association of baseline higher platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios with less durable radiographic response to immune checkpoint inhibitors in non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21137 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21137-e21137

Author(s):

Yenong Cao ◽

John P. Palmer ◽

Samer Ibrahim ◽

Natasha Dhawan ◽

Muhammad Zubair Afzal ◽

...

Keyword(s):

Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Response Rate ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

Radiographic Response ◽

Line Therapy ◽

Nsclc Patients

e21137 Background: Immune checkpoint inhibitors (ICI) are the standard of care in the treatment of non-small cell lung cancer (NSCLC). ICIs are commonly used in combination with chemotherapy but may be used as monotherapy in selected cases. Registration trials have shown a response rate of 40–50% in such patients and a durable response in some patients. However, there are no reliable predictive markers that determines the response and its durability. Recruitment of the inflammatory cells in the tumor microenvironment (TME) can determine the response to ICIs and an increased inflammatory state can be a poor prognostic factor. Peripheral inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can reflect the inflammatory changes within the TME. We aim to study the effect of high NLR and PLR on the radiographic response and its durability in NSCLC patients treated with ICIs. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs such as pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab either alone or in combination with chemotherapy. Radiographic response, and the duration of radiographic response (date of best response to radiographic progression), NLR, and PLR were calculated at baseline and 8 weeks since the start of ICI. High NLR and PLR was defined as greater than the median NLR and PLR values. Cox regression univariate and multivariate analyses were performed. Logistic regression and Chi-square tests were applied. Results: Overall 81% patients had adenocarcinoma and 19% patients had squamous, adenosquamous or large cell carcinoma. Majority of the patients were female (56.2% vs. 43.8%). The objective response rate (ORR) was 45.1% and the disease control rate (DCR) was 75.8%. The ORR was 51% in patients receiving ICI as first line therapy compared to 35% in patients who received ICI as a second line therapy. There was statistically significant difference in median duration of response in patients with high vs. low NLR (9.8 months vs. 18 months, P = 0.01, 95% CI 10.9– 26.2) and high vs. low PLR (9.0 months vs. 17 months, P = 0.03 95% CI 10.9–24.33) at baseline. The baseline odds ratio (OR) of response in the high NLR and high PLR group was 0.73 (P = 0.5, 95% CI 0.36–1.64) and 0.63 (P = 0.2, 95% CI 0.32–1.23), respectively. However, the odds to respond to ICI decreased significantly in patients with high NLR and PLR at 8 weeks [NLR (OR = 0.16, P = 0.0001, 95% CI 0.06–0.43)] and [PLR (OR = 0.27, P = 0.005, 95% CI 0.1–0.6). Conclusions: NLR and PLR may be reliable surrogate markers determining the durability of response to ICI in NSCLC patients. Standard imaging studies and serial monitoring may be beneficial to monitor the response to ICIs. However, prospective studies are needed to develop predictive and prognostic models utilizing these indices.

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Immune Checkpoint Inhibitors and Cardiac Toxicity in Patients Treated for Non-Small Lung Cancer: A Review

International Journal of Molecular Sciences ◽

10.3390/ijms21197195 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7195 ◽

Cited By ~ 1

Author(s):

Grzegorz Sławiński ◽

Anna Wrona ◽

Alicja Dąbrowska-Kugacka ◽

Grzegorz Raczak ◽

Ewa Lewicka

Keyword(s):

Lung Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Clinical Manifestations ◽

Treatment Strategies ◽

Life Threatening ◽

Underlying Mechanisms

Lung cancer is a major cause of cancer-related mortality worldwide, both in men and women. The vast majority of patients are diagnosed with non-small-cell lung cancer (NSCLC, 80–85% of lung cancer cases). Therapeutics named immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. They are monoclonal antibodies, and those directed against PD-1 (programmed cell death protein 1) or PD-L1 (programmed cell death-ligand 1) have been used in the treatment of lung cancer and significantly improved the prognosis of NSCLC patients. However, during treatment with ICIs, immune-related adverse events (irAEs) can occur in any organ and any tissue. At the same time, although cardiac irAEs are relatively rare compared to irAEs in other organs, they have a high mortality rate. The two most common clinical manifestations of immunotherapy-related cardiotoxicity are myocarditis and pericarditis. Various types of arrhythmias have been reported in patients treated with ICIs, including the occurrence of life-threatening complete atrioventricular block or ventricular tachyarrhythmias. Here, we aim to summarize the incidence, clinical manifestations, underlying mechanisms, diagnosis, and treatment strategies for ICI-associated cardiotoxicity as these issues become very important in view of the increasing use of ICI in the treatment of lung cancer.

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