Bi-cytopenia possibly induced by anti-PD-1 antibody for primary malignant melanoma of the esophagus

Abstract

Background:Anti-programmed cell death 1 antibody nivolumab is a promising agent for various cancers. Immune-related adverse events are recognized; however, bi-cytopenia with nivolumab has not been reported.Case presentation:A 73-year-old man was diagnosed with advanced primary malignant melanoma of the esophagus with liver, lung, and lymph node metastases. Previous therapies including dacarbazine and radiation of 39 Gy to the esophageal region were performed, but the liver metastases deteriorated. The patient was then administered nivolumab (2 mg/kg, every 3 weeks). After 3 cycles, the esophageal tumor and lymph nodes showed marked reductions in size, the lung metastases disappeared, and the liver metastases shrank partially. The treatment continued with 7 cycles for 4 months. However, severe anemia and thrombocytopenia appeared in the 6th cycle, and intermittent blood transfusions were required. The patient received high-dose intravenous methylprednisolone therapy for bi-cytopenia, but it was ineffective. Seven months after the initiation of nivolumab, the patient died of tumor. Although the mechanisms of bi-cytopenia were unclear, it could have been induced by nivolumab.Conclusion:The present case shows a rare but serious life-threatening bi-cytopenia possibly associated with nivolumab and suggests the importance of awareness of hematological adverse events during nivolumab therapy.

Pembrolizumab‐induced pancytopenia in a patient with squamous cell lung cancer

“…We identified 19 reports of hematological adverse events related to pembrolizumab or nivolumab. [8][9][10][11][12][13][14][15][16][17] Seven reports were related to pembrolizumab. [2][3][4][5][6][7] Only three reports described pancytopenia, including the present report (Table 1).…”

Pembrolizumab-Induced Pancytopenia: A Case Report

“…8 Schwab et al 9 and Kong et al 10 each described a case of autoimmune hemolytic anemia associated with nivolumab that responded appropriately to corticosteroids. Inadomi et al 11 described a patient in whom bicytopenia developed after nivolumab therapy: Grade 4 anemia and Grade 4 thrombocytopenia. The patient received intravenous methylprednisolone treatment and RBC and platelet transfusions, but his bicytopenia did not recover, and he eventually died.…”

“…[1][2][3] Immune-mediated hematologic toxicity could vary from anemia, thrombocytopenia, and leukopenia to rarely pancytopenia (Table 1). [4][5][6][7][8][9][10][11][12][13][14] We present the first case, to our knowledge, of pembrolizumab-induced pancytopenia to be reported in the literature.…”

A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with PD1-Blocking Agents for Metastatic Melanoma

“…To date, only a few cases of immune thrombopenia resulting from therapy with checkpoint inhibitors have been published [7][8][9][10]. However, in large prospective clinical trials investigating checkpoint inhibitors in different malignancies, 'cytopenia' was reported with an incidence between 5 and 17% [9].…”

“…However, all of these drugs may induce autoimmune phenomena such as thyroid dysfunction, vitiligo, rash, autoimmune colitis, or pneumonitis [5,6]. Cases of severe forms of autoimmune-mediated thrombocytopenia have been reported in singular cases only [7][8][9][10].…”