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Successful treatment of steroid-refractory immune checkpoint inhibitor-related pneumonitis with triple combination therapy: a case report

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Abstract

Immune checkpoint inhibitor (ICI)-related pneumonitis is a relatively rare but clinically serious and potentially life-threatening adverse event. The majority of cases can be managed by drug discontinuation, with the administration of corticosteroids added in severe cases. However, worsening of pneumonitis can develop in a subset of patients despite treatment with high doses of corticosteroids. We herein report a case of steroid-refractory ICI-related pneumonitis in a recurrent non-small cell lung cancer (NSCLC) patient treated with pembrolizumab that was successfully improved by triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide). After 3 weeks of initial pembrolizumab administration, the patient was diagnosed with ICI-related pneumonitis. Chest computed tomography (CT) showed patchy distributed bilateral consolidation and ground-glass opacities (GGOs) with traction bronchiectasis and bronchiolectasis resembling the diffuse alveolar damage (DAD) radiographic pattern. Although methylprednisolone pulse therapy was initiated, worsening of respiratory failure resulted in the patient being transferred to the intensive care unit. Because of an insufficient therapeutic response to high-dose corticosteroids, tacrolimus and cyclophosphamide pulse therapy were additively performed as triple combination therapy according to the treatment strategy for pulmonary complications of clinically amyopathic dermatomyositis (CADM). In response to this triple combination therapy, the patient’s respiratory condition gradually improved, and chest CT showed the marked amelioration of pulmonary opacities. This is the first report suggesting the efficacy of triple combination therapy (high-dose corticosteroids, tacrolimus, and cyclophosphamide) for steroid-refractory ICI-related pneumonitis complicated with respiratory failure.

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Abbreviations

AIP:

Acute interstitial pneumonia

ALK:

Anaplastic lymphoma kinase

BAL:

Bronchoalveolar lavage

BNP:

B-type natriuretic peptide

CADM:

Clinically amyopathic dermatomyositis

CI:

Confidence interval

COP:

Cryptogenic organizing pneumonia

CT:

Computed tomography

CTCAE:

Common Toxicity Criteria for Adverse Events

CTLA-4:

Cytotoxic T-lymphocyte antigen 4

DAD:

Diffuse alveolar damage

DM:

Dermatomyositis

EGFR:

Epidermal growth factor receptor

GGO:

Ground-glass opacities

HFNC:

High-flow nasal cannula

HP:

Hypersensitivity pneumonia

ICI:

Immune checkpoint inhibitor

ICU:

Intensive-care unit

ILD:

Interstitial lung disease

irAE:

Immune-related adverse event

KL-6:

Krebs von den Lungen-6

MDA 5:

Melanoma differentiation-associated gene 5

NSCLC:

Non-small cell lung cancer

NSIP:

Nonspecific interstitial pneumonia

PD-1:

Programmed cell death 1

PD-L1:

Programmed cell death ligand 1

PM:

Polymyositis

ROS1:

C-ros oncogene 1

SP-D:

Surfactant protein-D

TNF-α:

Tumor necrosis factor alpha

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Funding

This study was not supported by any funding.

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Authors and Affiliations

  1. Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, 3-19-18 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Hirofumi Utsumi, Jun Araya, Keitaro Okuda, Junko Watanabe, Daisuke Takekoshi, Yu Fujita, Mitsuo Hashimoto, Hiroshi Wakui, Shunsuke Minagawa, Takanori Numata, Hiromichi Hara & Kazuyoshi Kuwano

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  1. Hirofumi Utsumi
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  2. Jun Araya
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  3. Keitaro Okuda
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  5. Daisuke Takekoshi
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  6. Yu Fujita
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  7. Mitsuo Hashimoto
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Contributions

HU and SM treated the patient. HU and JA wrote the case report. All authors made substantial contributions to data interpretation, discussion, manuscript preparation, review and revision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hirofumi Utsumi.

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Written informed consent was obtained from the patient for publication of this case report.

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Utsumi, H., Araya, J., Okuda, K. et al. Successful treatment of steroid-refractory immune checkpoint inhibitor-related pneumonitis with triple combination therapy: a case report. Cancer Immunol Immunother 69, 2033–2039 (2020). https://doi.org/10.1007/s00262-020-02600-0

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  • DOI: https://doi.org/10.1007/s00262-020-02600-0

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