Anti–PD-1 Inhibitor–Related Pneumonitis in Non–Small Cell Lung Cancer

Nishino, Mizuki; Chambers, Emily S.; Chong, Curtis R.; Ramaiya, Nikhil H.; Gray, Stacy W.; Marcoux, Judith; Hatabu, Hiroto; Jänne, Pasi A.; Hodi, F. Stephen; Awad, Mark M.

doi:10.1158/2326-6066.cir-15-0267

Cited by 134 publications

(120 citation statements)

References 18 publications

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“…To the best of our knowledge, this is the first case‐control study systematically seeking to identify risk factors for anti‐PD‐1 mAbs‐related pneumonitis development in a Chinese population of multiple types of advanced cancer. This study fills an important gap in the literature and supplements the limited number of published reports on anti‐PD‐1 pneumonitis 5, 16, 17, 18…”

Section: Discussionsupporting

confidence: 72%

Risk factors for pneumonitis in patients treated with anti‐programmed death‐1 therapy: A case‐control study

Cui

Liu

Wang³

et al. 2018

Cancer Medicine

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Immune checkpoint blockade‐related pneumonitis is a rare but potentially life‐threatening adverse effect, but its risk factors are not completely understood. This case‐control study was conducted to identify pneumonitis risk factors in patients treated with anti‐PD1 monoclonal antibodies (mAbs), including all the patients who developed pneumonitis after anti‐PD‐1 mAbs treatment in the Cancer Center of the Chinese People's Liberation Army from September 2015 to September 2017. Two controls per case were matched according to a propensity‐score matching algorithm to account for confounding effects caused by individual baseline variables. Demographic and clinical information was obtained from medical records. In total, 55 cases and 110 controls were included in the study. No association was observed between smoking status or primary lung cancer and risk of pneumonitis. Significant risk factors for pneumonitis related to anti‐PD‐1 mAbs were prior thoracic radiotherapy, prior lung disease and combination therapy with odds ratios of 3.34 (1.51‐7.39), 2.86 (1.45‐5.64) and 2.73 (1.40‐5.31), respectively. The associations remained significant in the multivariable logistic regression model. The risk of pneumonitis induced by anti‐PD‐1 mAbs is associated with prior thoracic radiotherapy, prior lung disease, and combination therapy. Clinicians should monitor these features in patients receiving anti‐PD‐1 therapy to optimize clinical safety and efficacy.

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Section: Discussionsupporting

confidence: 72%

Risk factors for pneumonitis in patients treated with anti‐programmed death‐1 therapy: A case‐control study

Cui

Liu

Wang³

et al. 2018

Cancer Medicine

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“…A 58-year-old man developing NSIP radiological pattern after only 7 weeks of therapy. Other data is provided by Nishino et al who found that in a population of 170 patients treated with nivolumab, alone or in combination with other immune checkpoint inhibitors, 20 patients (11%) developed pneumonitis [7]. The international clinical trials concluded low risk of DILD after treatment with nivolumab, pembrolizumab and docetaxel [8][9][10][11][12], but these results will presumably prove to be underestimated after 2 years follow-up.…”

Section: Casementioning

confidence: 99%

“…The panorama of treatment options includes new immunotherapeutic drugs, approved for lung cancer therapy. These molecules enhance anti-tumor immunity by inhibiting negative T cell regulators and programmed cell-death-1 [4][5][6][7][8][9][10]. Immune checkpoint inhibitors currently approved for treatment of advanced NSCLC include nivolumab (anti CTLA-4 and anti PD1), pembrolizumab (anti PD1) and atezolizumab (anti PDL-1) [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…These molecules enhance anti-tumor immunity by inhibiting negative T cell regulators and programmed cell-death-1 [4][5][6][7][8][9][10]. Immune checkpoint inhibitors currently approved for treatment of advanced NSCLC include nivolumab (anti CTLA-4 and anti PD1), pembrolizumab (anti PD1) and atezolizumab (anti PDL-1) [7,8]. Despite encouraging results, these drugs seem associated with autoimmune-like toxicities, such as pneumonitis, in 3-10% of cases [9,11,12].…”

Section: Introductionmentioning

confidence: 99%

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Fibrotic lung toxicity induced by cytotoxic drugs, radiation and immunotherapy in patients treated for lung cancer

Bargagli¹,

Bonti²,

Bindi

et al. 2018

Monaldi Arch Chest Dis

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Patients treated for lung cancer may develop lung toxicity induced by chemotherapy (DILD), radiation or combined radiation recall pneumonitis. In the literature, some cases of immune-mediated pneumonitis have been reported associated with immunotherapy. The clinical and radiologic features of interstitial lung toxicity are unspecific, dyspnea and dry cough are the most common symptoms while the most frequent radiological pattern is the cryptogenic organizing pneumonia (COP). Why only some individuals treated with these drugs develop interstitial lung toxicity is unclear. Old age, ethnicity, doses, drug interactions, oxygen damage and radiation therapy are known risk factors, as well as pre-existing lung disease. There are no clear indicators of the risk of developing lung toxicity secondary to drugs or radiation for individual patients. In the last few years some studies have reported the utility of KL 6 for the evaluation of DILD. The treatment is based on high doses of systemic steroids or immune suppressor. In this study we report severe interstitial lung damage in patients treated with different anti-blastic, immune and radiation therapies. Treated with surgery, chemotherapy, immuno-and radiotherapy for lung cancer, they unfortunately died of severe DILD.

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“…There is no apparent relationship to tumor type treated, as pneumonitis cases have been observed in studies with multiple tumor types, including melanoma and lung and kidney cancers, although it has been suggested that pneumonitis presents more often when anti-PD-1 agents are used in patients with lung cancer than melanoma (39,43,44). Pneumonitis symptoms include cough, shortness of breath, dyspnea and fever and often involve only asymptomatic radiographic changes.…”

Section: Pneumonitismentioning

confidence: 99%

Toxicity management of immunotherapy for patients with metastatic melanoma

Linardou¹,

Gogas²

2016

Ann. Transl. Med.

102

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Checkpoint inhibitors have revolutionized the treatment of patients with metastatic melanoma offering improved responses and significant survival benefit. These agents are now approved for the treatment of metastatic melanoma, squamous and non-squamous non-small cell lung cancer (NSCLC) and kidney cancer, while they are now being investigated in a range of other malignancies. In addition, another anti-PD-L1 monoclonal antibody (atezolizumab) was recently approved for urothelial cancer. Ipilimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody and the anti-PD-1 agents nivolumab and pembrolizumab have followed large clinical development programs, therefore, information regarding their safety and toxicity profile is readily available. Unique toxicities have been observed, which stem from and relate to the immune activation by these agents and are thus termed as immune-related adverse events (irAEs). Clinicians and patients should be aware of this different toxicity profile, so as to promptly recognize, identify and manage symptoms related to irAEs. Indeed, clinical experience has shown that these immune events, when they are early recognized and timely managed, are mostly reversible otherwise they can evoke severe or even life-threatening situations. Several recommendations and guidelines have been developed for the management of irAEs and algorithms have been published based primarily on our knowledge from the ipilimumab trials.

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Anti–PD-1 Inhibitor–Related Pneumonitis in Non–Small Cell Lung Cancer

Cited by 134 publications

References 18 publications

Risk factors for pneumonitis in patients treated with anti‐programmed death‐1 therapy: A case‐control study

Risk factors for pneumonitis in patients treated with anti‐programmed death‐1 therapy: A case‐control study

Fibrotic lung toxicity induced by cytotoxic drugs, radiation and immunotherapy in patients treated for lung cancer

Toxicity management of immunotherapy for patients with metastatic melanoma

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