Bicytopenia in Primary Lung Melanoma Treated with Nivolumab

Abstract

A 73-year-old man who was a current smoker complained of weakness in his limbs and slow movement and was diagnosed with primary lung melanoma with brain metastases. Following stereotactic brain radiotherapy, nivolumab was administrated. After the first cycle of nivolumab, his blood neutrophil count and hemoglobin levels started to decline. Excluding other possible causes, nivolumab was considered the most probable cause of bicytopenia. Nivolumab was not restarted, and the bicytopenia gradually recovered with no corticosteroid administration for this event. While serious hematological adverse events regarding immune checkpoint inhibitors have been assumed to be rare, severe neutropenia and anemia should be considered in patients receiving immune checkpoint therapy.

Challenges in diagnosis and management of neutropenia upon exposure to immune-checkpoint inhibitors: meta-analysis of a rare immune-related adverse side effect

“…As a consequence of the retrospective nature of the data, possibly under-reported co-medications, and the inconsistent supportive treatment approaches, the duration of ICI-induced neutropenia must be interpreted with caution. Overall, 76% of the cases achieved a normalization of the neutrophils, which is in line with the finding of the published results of Finkel et al [33], who have done a comparable analysis of 20 overlapping patients with our cohort [9,15,17,18,21,25,27]. Focusing on irAEs, they are suggested to arise from general immunologic enhancement and are often manageable by discontinuation of the ICI therapy and/or treatment with immunosuppressive drugs [34].…”

Immunotherapy-induced severe neutropenia with neurotoxicity: A case of a 75-year-old woman with ulcerative colitis diagnosed with melanoma

“…Of the 313 patients receiving nivolumab, there was one treatment-related death from neutropenia. 9 There are a few case reports of nivolumab-induced neutropenia 11,12 in addition to cases of nivolumab resulting in thrombocytopenia, 13 leukocytopenia, 14 bi-cytopenia, 15 and pancytopenia. 16 In most of these cases, neutropenia gradually recovered with intravenous methylprednisolone and/or IVIG.…”

“…Most other cases in the literature reported an earlier onset of neutropenia, after two to six doses of nivolumab, but there were two other cases involving a delayed onset. [11][12][13][14][15][16] In one case of a patient on nivolumab for lung adenocarcinoma, the patient did not develop significant neutropenia until prior to their 12th dose at which point nivolumab was discontinued and steroid therapy initiated. The patient was unable to be tapered off steroids due to recurrent severe neutropenic events and after a year of nivolumab discontinuation, passed away.…”

“…The incidence of neutropenia from nivolumab is less than 1% 9,10 and described in only a few case reports. [11][12][13][14][15][16] Here, we describe a case of refractory neutropenia in a patient with a history of ulcerative colitis and stage III melanoma on adjuvant nivolumab.…”

Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors

“…Pancytopenia has also been reported and is associated with nivolumab (Opdivo) and ipilimumab ( Rusquec et al, 2014 ; Tokumo et al, 2018 ). Some authors indicate that cytopenias are often late occurrences; however, others report the cytopenias occurring early in treatment ( Rusquec et al, 2014 ; Takahashi et al, 2019 ).…”