Severe pneumonitis refractory to steroids following anti-PD-1 immunotherapy

Anti-programmed death 1 (PD-1) immune checkpoint inhibitors enhance the antitumour activity of the immune system and have produced durable tumour responses in several solid tumours including non-small cell lung cancer (NSCLC). However, PD-1 inhibitors can lead to immune-related adverse events , including pneumonitis, which is typically mild, but can be severe and potentially fatal. Pneumonitis often resolves with steroids, but some cases are steroid refractory, leading to a relapsing and remitting course in milder cases or the need for salvage therapies in more severe cases. Here, we present two patients with NSCLC who developed severe pneumonitis following therapy with nivolumab and pembrolizumab. While one patient improved with steroids and infliximab, the other patient failed to respond to steroids and subsequently died. These cases demonstrate the highly variable presentation and therapeutic responses seen in patients with pneumonitis following anti-PD-1 therapy and illustrate that severe cases can often present refractory to steroid therapy.

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Advancing the Management of Non-small Cell Lung Cancer

European Oncology & Haematology ◽

10.17925/eoh.2017.13.01.53 ◽

2017 ◽

Vol 13 (01) ◽

pp. 53

Author(s):

David F Fakih ◽

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

Programmed Death ◽

Programmed Death 1 ◽

Personalised Therapy

Advances in the development of targeted therapies and immunotherapy have transformed the management of non small-cell lung cancer (NSCLC). Targeting angiogenesis and molecular drivers of carcinogenesis has led to the approval of several new therapies. More recently, immunotherapeutic approaches have been investigated in the treatment setting of NSCLC. These include immune checkpoint inhibitors (e.g. anti-cytotoxic T-lymphocyte antigen-4 [CTLA-4], anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 [PD-L1] agents). The emergence of so many therapeutic options offers the potential for personalised therapy. Molecular profiling can inform treatment decisions but there is a need for more data to determine the optimal sequencing and combination of targeted and immunotherapeutic agents.

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Nivolumab-induced adrenalitis

BMJ Case Reports ◽

10.1136/bcr-2019-231829 ◽

2019 ◽

Vol 12 (11) ◽

pp. e231829 ◽

Cited By ~ 4

Author(s):

Iqra Iqbal ◽

Muhammad Atique Alam Khan ◽

Waqas Ullah ◽

Dina Nabwani

Keyword(s):

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Death Receptor ◽

Small Cell ◽

Second Line ◽

Small Cell Lung ◽

Programmed Death Ligand 1 ◽

Programmed Death ◽

Life Threatening ◽

Line Chemotherapy

Immune checkpoint inhibitors (ICIs) are an evolving class of drugs for the treatment of various cancers; for example, their use is recommended as a second-line chemotherapy for non-small cell lung cancer. With the expanding use of ICIs, we are discovering their unique side effects, called immune-related adverse events (irAEs), which can impair gastrointestinal, hepatic, dermatological, endocrine and other systems. Nivolumab is an ICI that blocks the human programmed death receptor-1 (PD-1) on T cells to prevent the interaction between the receptor, PD-1, and human programmed death ligand-1 expressed on tumour cells. Here, we report a case of a 65-year-old woman with recurrent lung adenocarcinoma who was treated with nivolumab and developed immune-related adrenalitis, which was managed with hydrocortisone and fludrocortisone. This case highlights the importance of understanding the irAEs of ICIs to allow prompt recognition and management of life-threatening complications of the treatment.

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Challenges of Immunotherapy in Stage IV Non–Small-Cell Lung Cancer

JCO Oncology Practice ◽

10.1200/op.20.00949 ◽

2021 ◽

pp. OP.20.00949

Author(s):

Sophie Stock-Martineau ◽

Kate Magner ◽

Kevin Jao ◽

Paul Wheatley-Price

Keyword(s):

Lung Cancer ◽

Lung Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Programmed Death

Treatment for metastatic non–small-cell lung carcinoma has seen important advances in recent years with the introduction of targeted therapies and immunotherapy. Immune checkpoint inhibitors, which target the programmed death 1 receptor and programmed death ligand-1, alone or in combination with platinum-based chemotherapy, have become standard of care in the first-line setting for patients with advanced non–small-cell lung carcinoma without targetable driver mutations. However, several clinical questions have now since emerged. Physicians treating lung cancer lack guidance when treating patients who have a poor performance status, patients who are receiving corticosteroids, and those known for pre-existing autoimmune disorders. Furthermore, data are scarce on rechallenging a patient with immune checkpoint inhibitors after the occurrence of a significant immune-related adverse event. In this review, we aim to shed light on these topics.

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Exploring Novel Immune-Related Toxicities and Endpoints with Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2013.33.e280 ◽

2013 ◽

pp. e280-e285 ◽

Cited By ~ 2

Author(s):

Laura QM Chow

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

Immune Mediated ◽

Programmed Death

Because of dramatic tumor regressions reported with the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PDL-1) antibodies inhibiting the PD-1 immune checkpoint, non-small cell lung cancer (NSCLC) is now recognized as an immune-modifiable disease. As responses were observed in smaller numbers in phase I trials, the immunologic profiles and unique toxicities of these agents have not been fully established in NSCLC. Moreover, PD-1 checkpoint inhibitors in development by different companies may demonstrate diverse spectrums of activity and toxicity. Although the cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors in earlier phase studies appeared to have less impressive responses in NSCLC, their safety profile has been more broadly defined. The anti-CTLA-4 antibody, ipilimumab, has the best characterized immune-related toxicities (predominantly skin, gastrointestinal, hepatic, and endocrine) and management strategies in melanoma. Despite the lack of studies directly comparing these agents, toxicities from PD-1 inhibition seem milder than those of CTLA-4 inhibition, with distinct toxicities of pneumonitis infrequently observed with the BMS-936558 anti-PD-1 antibody, nivolumamb, and frequent mild infusion reactions reported with the BMS-936559 anti-PDL-1 antibody. As lungs are critical organs often already compromised in NSCLC patients, immune-mediated pneumonitis can cause worrisome morbidity and mortality. Even though immune checkpoint inhibitors are being rapidly developed in a multitude of trials, optimal immune-mediated toxicity management has not been determined, is evolving, and will be further explored. Early diagnosis and symptom management with corticosteroids form the basis of treatment. Assessment of new immune-response criteria and use of primary endpoints of overall survival (OS) will be important in the development of these immunotherapies in NSCLC.

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Tracking the tail

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-000971 ◽

2020 ◽

Vol 8 (2) ◽

pp. e000971

Author(s):

Alex Friedlaender ◽

Stephen V Liu ◽

Alfredo Addeo

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Current Data ◽

Small Cell ◽

Front Line ◽

Small Cell Lung ◽

Programmed Death

Immune-checkpoint inhibitors have deeply changed the therapeutic landscape of advanced non-small cell lung cancer without actionable genomic alterations. Immune-checkpoint inhibitors have become standard front-line therapy, especially among patients with tumours expressing high levels of programmed death ligand-1; yet, many patients do not respond to therapy. This has led to the adoption of front-line combination therapies, administering programmed death-1 inhibitors concomitantly either with other checkpoint inhibitors, chemotherapy or both. Today’s approved standard of care includes options with chemoimmunotherapy or dual checkpoint blockade, but each combination has only been compared to chemotherapy alone and no head-to-head trials exist. In cross-trial comparisons, combinations trials appear to show numerically superior responses to single-agent checkpoint inhibitors but the question is whether they ultimately offer a survival advantage. In this manuscript, we summarize and analyse all currently available front-line immune-checkpoint inhibitor trials in non-small cell lung cancer, whether as monotherapy or in combination with chemotherapy, second immunotherapy agents or both. Should standards of care change given the current data? While we ponder this question, we illustrate current data and conclude that the answer lies in tracking the tail of the survival curves.

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