Idiopathic thrombocytopenic purpura and autoimmune neutropenia induced by prolonged use of nivolumab in Hodgkin’s lymphoma

Bulbul, Ajaz; Mustafa, A.; Chouial, S; Rashad, Sadaf

doi:10.1093/annonc/mdx159

Cited by 26 publications

(22 citation statements)

References 5 publications

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“…AIHA is not the only yet rare hematologic complication of CPIs. Several cases of autoimmune neutropenia, thrombocytopenia, and even pancytopenia were recently published …”

Section: Discussionmentioning

confidence: 99%

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Autoimmune hemolytic anemia associated with the use of immune checkpoint inhibitors for cancer: 68 cases from the Food and Drug Administration database and review

Tanios

Doley

Munker

2018

European J of Haematology

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Background Immune checkpoint inhibitors (CPI) are widely used in modern oncology and have improved the prognosis of lung cancer, malignant melanoma, and other malignancies. Unlike cytotoxic chemotherapy, drugs such as nivolumab, pembrolizumab, and ipilimumab are associated with immune‐related adverse effects. We recently observed a patient with lung cancer who developed a fulminant warm antibody autoimmune hemolytic anemia (AIHA). Objectives Investigate the frequency and prognosis of AIHA secondary to CPI in a public database and review the literature. Results A total of 68 cases were identified in the database of the Food and Drug Administration (FDA), 43 were associated with nivolumab, 13 with pembrolizumab, seven with ipilimumab, and five with atezolizumab. All episodes of AIHA were listed as serious. If the total number of adverse events cases reported to the FDA is taken as a reference, AIHA is rare, but occurred more frequently with PD‐1 or PD‐L1 targeting agents (0.15%‐0.25%) than with CTLA‐4 inhibitors (0.06%). In addition to our case, the literature review identified 11 similar cases. Most cases of AIHA responded to steroids, but two of 12 were fatal. Conclusion We describe AIHA as a new and serious immune‐related side effect of CPI. Early aggressive management is necessary.

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“…AIHA is not the only yet rare hematologic complication of CPIs. Several cases of autoimmune neutropenia, thrombocytopenia, and even pancytopenia were recently published …”

Section: Discussionmentioning

confidence: 99%

“…Several cases of autoimmune neutropenia, thrombocytopenia, and even pancytopenia were recently published. 34,35 Because of the somewhat limited experience with CPIs and the low prevalence of AIHA, treatment of CPI-induced AIHA is still presumptive. We recommend, based on the literature ( were followed for a mean of 46 ± 40 months.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune hemolytic anemia associated with the use of immune checkpoint inhibitors for cancer: 68 cases from the Food and Drug Administration database and review

Tanios

Doley

Munker

2018

European J of Haematology

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“…Several case reports have described nivolumab-induced blood cell reduction (11-16), including a case with bicytopenia (15, 16). In those reports, cases of autoimmune hemolytic anemia (13, 14) and autoimmune neutropenia (16) were described.…”

Section: Discussionmentioning

confidence: 99%

Bicytopenia in Primary Lung Melanoma Treated with Nivolumab

et al. 2019

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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.

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“…However, some reports have documented the PD-1 antibody nivolumab causing severe neutropenia or opportunistic infections. 12–15) Wang et al 16) reported that nivolumab caused immunosuppressive regulation, possibly due to feedback mediated by blockade of the PD-1/PD-L1 signaling pathway. We thus speculated that the brain metastasis formed first, then PD-L1 blockade and subsequent immunosuppressive regulation might have promoted abscess formation at the same site in this case.…”

Section: Discussionmentioning

confidence: 99%

Abscess Formation in Metastatic Brain Tumor with History of Immune Checkpoint Inhibitor: A Case Report

Takayasu

Yamasaki

Shishido

et al. 2019

NMC Case Report Journal

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We present the case of a 68-year-old man with brain metastasis from lung cancer and a history of immune checkpoint inhibitor administration, with overlapping abscess within the metastatic lesion. He initially received antibiotic treatment under a diagnosis of brain abscess because of a hyper-intense area on diffusion-weighted imaging inside the gadolinium-enhanced wall. The size of the enhanced lesion did not change much, but the extent of perifocal edema decreased after antibiotic treatment. After 2–4 months, the lesion gradually enlarged, and imaging characteristics changed from single cyst to multiple cysts. Surgical resection was performed and pathological examination revealed the lesion as metastasis from the lung tumor. Smear preparation of the tumor contents detected Gram-positive bacilli, confirming the dual pathology of metastasis and brain abscess. Discussing the pathogenesis, we speculated that therapy with durvalumab (MEDI4736), an anti-PD-L1 antibody, induced immune status modification including immunosuppressive regulation, which might have promoted abscess formation.

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Idiopathic thrombocytopenic purpura and autoimmune neutropenia induced by prolonged use of nivolumab in Hodgkin’s lymphoma

Cited by 26 publications

References 5 publications

Autoimmune hemolytic anemia associated with the use of immune checkpoint inhibitors for cancer: 68 cases from the Food and Drug Administration database and review

Autoimmune hemolytic anemia associated with the use of immune checkpoint inhibitors for cancer: 68 cases from the Food and Drug Administration database and review

Bicytopenia in Primary Lung Melanoma Treated with Nivolumab

Abscess Formation in Metastatic Brain Tumor with History of Immune Checkpoint Inhibitor: A Case Report

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