Immune-Mediated Thrombocytopenia and Hypothyroidism in a Lung Cancer Patient Treated with Nivolumab

Abstract

Patients treated with immune checkpoint inhibitors can develop various immunological complications; however, few cases of immune thrombocytopenia occurring in association with the administration of these agents have so far been reported. We herein report the case of a 62-year-old Japanese man with non-small-cell lung cancer who developed immune thrombocytopenia and hypothyroidism during nivolumab therapy. After the second administration of the drug, his peripheral blood platelet count rapidly decreased to 1.6 × 10/μl with a petechial rash and symptoms associated with a low thyroid function. Nivolumab-induced immune thrombocytopenia and hypothyroidism were suspected based on the presence of platelet-associated IgG, an increased level of autoantibodies to thyroglobulin and thyroid peroxidase and an enlarged thyroid gland. The patient eventually made a full recovery after treatment with oral prednisolone and levothyroxine. Further investigations and the accumulation of data are necessary to elucidate the precise mechanisms underlying the autoimmune responses that occur in patients treated with immune checkpoint inhibitors.

Severe Thrombocytopenia Associated With Pembrolizumab in Patients With Non-small Cell Lung Cancer (NSCLC): A Case Report and Literature Review

“…Aside from the current case, three cases have been identified as severe thrombocytopenia associated with anti-PD-1 antibody in patients with advanced NSCLC (1-3). Corticosteroid therapy was described as effective in previously reported cases of thrombocytopenia associated with irAEs, but there are still unknown data about the therapeutic significance of further immunosuppressive drugs or intravenous immunoglobulin (1)(2)(3)(4)(5)(6)(7)(8). Among the nine patients who experienced severe thrombocytopenia as an irAE, seven exhibited improved myelosuppression, while the other two died.…”

“…This is an extremely rare case of severe thrombocytopenia associated with pembrolizumab use. Several reports have described the management and occurrence of severe thrombocytopenia after ICI administration in patients with different neoplasms (1)(2)(3)(4)(5)(6)(7)(8). Table I shows the clinical features of patients with severe thrombocytopenia related to anti-PD-1/PD-L1 antibodies.…”

“…Among the nine patients who experienced severe thrombocytopenia as an irAE, seven exhibited improved myelosuppression, while the other two died. Given that severe thrombocytopenia as an irAE can become a dismal situation, early and appropriate treatment should be performed (1)(2)(3)(4)(5)(6)(7)(8). Since the relationship between ICI efficacy and thrombocytopenia was unknown in five out of nine patients, it remains unclear whether thrombocytopenia as an irAE could predict ICI efficacy (1)(2)(3)(4)(5)(6)(7)(8).…”

“…Myelosuppression is a common toxicity associated with cytotoxic chemotherapy, but it is relatively rare in patients with advanced non-small cell lung cancer (NSCLC) who received molecular targeting therapy or ICI. Several researchers have reported the potential of severe thrombocytopenia secondary to anti-PD-1/PD-L1 antibodies in cases of NSCLC or malignant melanoma (1)(2)(3)(4)(5)(6)(7). As a first palliative therapy for the immunerelated toxicity of severe thrombocytopenia, corticosteroids are chosen to avoid immunological reactions in the bone marrow; if not effective, immunosuppressive agents or immunoglobulin are sequentially added to increase the platelet count (1)(2)(3)(4)(5)(6)(7)(8).…”

Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma

“…As it occurs with other irAEs, the pathogenesis of haematologic irAEs is largely unknown, although autoantibody production may be an underlying mechanism as plateletassociated autoantibodies are frequently detected in patients with thrombocytopenia. 101 Haematologic disorders associated with chronic liver disease Cytopenias are common in chronic liver diseases. Portal hypertension may produce congestive splenomegaly with increased intrasplenic sequestration and destruction of blood cells, particularly when associated with portal vein thrombosis or tumour invasion by HCC.…”