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

Discussion

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 (1-8). Table I shows the clinical features of patients with severe thrombocytopenia related to anti-PD-1/PD-L1 antibodies. 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 (1-8). 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 (1-8). 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 (1-8). In NSCLC, however, two out of four patients with NSCLC demonstrated a partial response to ICIs (1-3). Some patients required an oral thrombopoietin receptor agonist to supplement the effects of a systemic steroid and immunoglobulin (2, 6). Moreover, little is known on the detailed mechanism by which PD-1 blockade treats thrombocytopenia. Almost all previously reported patients [8/9 (89%)] were male, but it remains unknown why severe thrombocytopenia as an irAE occurs primarily in males. Hematological disorders, viral or bacterial infections, collagen diseases, productive diseases of thrombosis, exhaustive diseases of the platelets, drug-induced diseases and unknown such as idiopathic thrombocytopenic purpura have been clarified as any diseases related to thrombocytopenia.

Regarding management, in patients with severe thrombocytopenia regardless of any disease or reason, a platelet transfusion should be considered to avoid the occurrence of intracranial hemorrhage. When thrombocytopenia persists for several weeks, steroid or intravenous IgG may be necessary. The management by platelet transfusion is a main issue in patients with severe thrombocytopenia secondary to cytotoxic chemotherapy, whereas, systemic steroid and immunoglobulin administration is identified as a reasonable choice in those due to immunotherapy (9-11).

Physicians should be alert to the potential of rare irAEs such as severe thrombocytopenia as described herein. An immediate administration of corticosteroids is necessary to successfully achieve irAE improvement after initiation of ICIs.