Immune thrombocytopenia induced by nivolumab in a patient with non-small cell lung cancer

Abstract

Antibodies targeting the receptor programmed death 1 on T cells have been approved for the treatment of lung cancer. Immune checkpoint inhibitors (ICIs) induce various immune-related adverse events. Life-threatening hematotoxicity can be provoked by ICI therapy. Although ICI-related endocrinopathy and interstitial lung disease have been well documented, hematotoxicity requiring intensive treatment is relatively rare. We describe a case of nivolumab induced thrombocytopenia after transient mild fever. A 77-year-old man with non-small cell lung cancer was administered nivolumab (240 mg/body, every 2 weeks) as second line therapy. On the day 2 after the first nivolumab infusion, he had a fever and his C-reactive protein level was elevated. Thoracic computed tomography revealed no interstitial lung disease or pneumonia. The fever resolved on day 9 and was not seen thereafter. On day 15 after the first nivolumab infusion, severe thrombocytopenia suddenly emerged. A bone marrow examination revealed no dysplasia or invasion. Based on the presence of high platelet-associated IgG titer, normal bone marrow plasticity and a lack of effectiveness of platelet infusion, we diagnosed nivolumab-induced immune thrombocytopenia. Daily administration of 60 mg of prednisolone restored the patient's platelet count and platelet-associated IgG. We also found that there was significant shrinkage of the primary lesion and that stable disease was achieved. One must be aware of this relatively rare side effect and the unusual clinical findings that could be associated with immunoreaction.

Nivolumab-induced immune thrombocytopenia in a patient with malignant pleural mesothelioma

“…Although any type of irAE was related to better outcomes of ICI treatment, analyses of the efficacy of ICIs in patients who develop hematological irAEs are limited. In a previous case report, tumor regression was observed in a patient with NSCLC who was treated with nivolumab and who developed nivolumab-induced ITP [ 24 ], which is comparable to the results in our case. The mechanism of the correlation between the outcome of ICI treatment and development of irAEs remains unknown; however, the shared antigen between tumor cells and normal cells might be responsible for the relationship between the outcome of ICI therapy and the development of irAEs [ 23 ].…”

Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance study from 2014 to 2019

“…Thrombocytopenia was the second most frequently reported hematological AE in the database. Besides the existing disproportionality signal reported in previous case reports and randomized controlled trials on nivolumab 24,25 and avelumab 26 monotherapy, we also detected thrombocytopenia disproportionality signal in atezolizumab and durvalumab monotherapy groups. Similar results were also observed in other hematological AEs, with variations in the class‐specific disproportionality signal.…”

Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitors in Solid Cancer: Case Report and Literature Review

“…In particular, when the irAEs concern platelets, it should be distinguished from a chemotherapy-induced thrombocytopenia for patients receiving chemotherapy plus immunotherapy because the prognosis and therapeutic management differs. Sometimes detecting the presence of a high platelet–associated IgG titer is helpful to confirm immune thrombocytopenia ( 8 ). Increased circulating PD-1+CD4+T cells and PD-L1+DCs and sPD-1 levels, which has been reported in idiopathic thrombocytopenic purpura, may be helpful in identifying immune-related thrombocytopenia ( 36 , 37 ).…”

“…Furthermore, a circulating immune response may contribute to a decreased thrombocyte count. In NSCLC cases, nivolumab induced or increased production of platelet-specific IgG autoantibodies that could promote platelet destruction with immature platelets and megakaryocytes without abnormal cells in a bone marrow biopsy ( 5 , 8 ). The pathogenesis of thrombocytopenia induced by ICIs is postulated to be similar to classical immune thrombocytopenia, including idiopathic thrombocytopenic purpura.…”