Nivolumab-related severe thrombocytopenia in a patient with relapsed lung adenocarcinoma: a case report and review of the literature

Abstract

Background: Immune checkpoint inhibitor therapy has changed the standard drug therapy for relapsed or advanced non-small cell lung cancer; its efficacy is well-recognized by pulmonary physicians, oncologists, and thoracic surgeons. Nivolumab, one of the anti-programmed cell death 1 antibodies, was the first immune checkpoint inhibitor to be approved and is used as a standard second-line regimen for patients with non-small cell lung cancer irrespective of the expression of programmed cell death ligand 1. Programmed cell death 1 antibodies have been generally confirmed to be less toxic than conventional cytotoxic chemotherapy, although unusual immune-related adverse events such as type I diabetes mellitus, adrenal failure, and myasthenia gravis may occur with a very low incidence. A case of severe grade V immune-related thrombocytopenia after two courses of nivolumab as second-line therapy for relapsed non-small cell lung cancer is reported.

Case presentation: An 82-year-old Japanese woman with relapsed lung adenocarcinoma was treated with nivolumab as second-line systemic therapy at our institute. Her laboratory data indicated thrombocytopenia suspected to be an immune-related adverse event following two courses of nivolumab. Subsequently, she developed a massive pulmonary hemorrhage and left cerebral infarction despite intensive treatment including systemic steroid therapy. Although there have been a few reports of thrombocytopenia caused by nivolumab, this is the first report of grade V thrombocytopenia following administration of nivolumab for relapsed non-small cell lung cancer.

Conclusion: A very difficult case of grade V immune-related thrombocytopenia after the administration of nivolumab as second-line therapy for relapsed lung adenocarcinoma was described. Immune-related thrombocytopenia is a rare adverse event, but it must be considered a possible complication because it may become critical once it has occurred.

Keywords: Immune checkpoint inhibitor; Immune-related thrombocytopenia; Nivolumab; Non-small cell lung cancer.

Fig. 1

Pathological findings of the resected specimen. a Hematoxylin and eosin staining shows invasive adenocarcinoma of papillary predominant type. b Immunohistochemistry was weakly positive for programmed cell death ligand 1 (PD-L1) (SP-142 antibody)

Fig. 2

Treatment timeline after relapse of cancer. Relapse of lung cancer was detected 7 months after surgery. First-line gefitinib was discontinued due to interstitial lung disease. Three months after gefitinib was stopped, nivolumab was begun as second-line therapy

Fig. 3

Clinical course of the present case. The platelet count recovers temporarily with intensive treatment, such as platelet transfusions, intravenous immunoglobulin, steroid pulse therapy, and romiplostim, but the patient’s general condition does not improve. IVIG intravenous immunoglobulin, P/F ratio partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, TRA thrombopoietin receptor agonist

Fig. 4

Chest X-ray, computed tomography findings, and immunohistochemistry at autopsy after thrombocytopenia. a Chest X-ray on admission for thrombocytopenia shows no noteworthy findings. b, c Chest X-ray and computed tomography scan at 24 days after admission show reduced bilateral permeability. d Immunohistochemistry at autopsy. CD8-positive tumor-infiltrating lymphocytes are focally positive, probably induced by nivolumab