Severe complicated neutropenia in two patients with metastatic non-small-cell lung cancer treated with nivolumab

Turgeman, Ilit; Wollner, Mira; Hassoun, Gamal; Bonstein, Lilach; Bar-Sela, Gil

doi:10.1097/cad.0000000000000520

Cited by 41 publications

(28 citation statements)

References 11 publications

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“…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].…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2020

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Background: Cancer immunotherapy via immune-checkpoint inhibition (ICI) by antibodies against cytotoxic Tlymphocyte-associated protein 4 (CTLA-4) and cell death protein 1 (PD-1) have significantly improved the outcome of metastasized melanoma and of a rapidly increasing number of other cancer types. The anti-tumor effect is often accompanied by immune-related adverse events (irAE). Hematological irAE, specifically neutropenia, are rarely observed. However, neutropenia is associated with high morbidity and mortality due to infection complications. Thus, early detection and treatment is crucial. Methods: We present the clinical course of two patients with severe neutropenia after ICI therapy and demonstrate the difficulty of the diagnosis when a comedication of metamizole, a well-known analgesic drug used to treat cancer pain, is present. Further, we provide a comprehensive descriptive and statistical analysis of published data on diagnostics, treatment and infection complication in patients with at least grade 4 neutropenia by a systematic database search. Results: Finally, 34 patients were analyzed, including the two case reports from our cohort. The median onset of neutropenia was 10.5 weeks after first ICI administration (interquartile range: 6 weeks). In 76% (N = 26), a normalization of the neutrophil count was achieved after a median duration of neutropenia of 13 days. In a subsample of 22 patients with detailed data, the infection rate was 13%, proven by positive blood culture in 3 cases, but 68% (N = 15) presented with fever > 38°C. Treatment regime differed relevantly, but mainly included G-CSF and intravenous corticosteroids. Death was reported in 14 patients (41%), 3 of whom (9%) were associated with hematological irAE but only two directly associated with neutropenia. Conclusion: With an increasing number of cancer patients eligible to ICI therapy, the incidence of severe hematological toxicities may rise substantially over the next years. Clinicians working in the field of cancer immune therapies should be aware of neutropenia as irAE to provide immediate treatment.

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Section: Discussionsupporting

confidence: 90%

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

et al. 2020

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“…Their impact on the immune system may be beneficial in countering the immunosuppressive microenvironment and does not cause immunosuppression by itself [26]. Few cases have reported on severe ICI-related neutropenia, mostly secondary to anti-CTLA4 agent Ipilimumab but the overall rate of grade 3-5 rate of neutropenia remains low around 0.94% (overall occurrence around 0.3-1.07%) while the incidence of febrile neutropenia was 0.54% [27][28][29][30][31]. A small series by Finkel et al analyzed the characteristics of 32 patients with immune-related neutropenia (irN).…”

Section: Immunosuppression and Icismentioning

confidence: 99%

Do checkpoint inhibitors compromise the cancer patients’ Immunity and Increase the Vulnerability to COVID-19 Infection?

Kattan

Assi

2020

Immunotherapy

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Since we are not able to consider ICIs treatment as highly immunosuppressive, avoiding it in cancer patients to reduce coronavirus infections could deprive these patients from a highly active class of drugs. "The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has been declared a pandemic by the WHO that claimed the lives of thousands of people within a few months. Cancer patients represent a vulnerable population due to the acquired immunodeficiency associated with anti-cancer therapy. Immune checkpoint inhibitors have largely impacted the prognosis of a multitude of malignancies with significant improvement in survival outcomes and a different, tolerable toxicity profile. In this paper, we assess the safety of ICI administration in cancer patients during the coronavirus pandemic in order to guide the usage of these highly efficacious agents.

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“…In another patient, although ICIs were not reused after granulocyte recovery, neutropenia recurred at eight weeks after remission but recovered again with the same treatment. [18][19][20][21][22][23][24] Aplastic anemia (AA) and pure red cell aplastic anemia (PRCA)…”

Section: Clinical Manifestationsmentioning

confidence: 99%

“…Other immune‐suppressing agents, including mycophenolate mofetil, cyclosporin A and anti‐thymocyte globulin (ATG) were administered to one patient with severe pancytopenia. In another patient, although ICIs were not reused after granulocyte recovery, neutropenia recurred at eight weeks after remission but recovered again with the same treatment …”

Section: Introductionmentioning

confidence: 99%

Clinical diagnosis and treatment recommendations for immune checkpoint inhibitor‐related hematological adverse events

Zhuang

Guo

et al. 2020

Thoracic Cancer

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Immune checkpoint inhibitors (ICIs) are able to reactivate the immune system, thereby enhancing the anti‐tumor effects. However, over‐activated T cells may induce immune‐related adverse events (irAEs). Hematological irAEs are rarely reported which mainly represent monolineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even life‐threatening diseases such as hemophagocytic lymphohistiocytosis. Here, the clinical manifestations of hematological irAEs are summarized and recommendations for diagnosis and treatment proposed. Key points Significant findings of the study• Hematological immune‐related adverse events (irAEs) caused by checkpoint inhibitors are rare and may sometimes be life‐threatening. This study summarizes the manifestations of hematological irAEs and proposes preliminary recommendations for diagnosis and treatment. What this study adds• Much still remains unknown regarding hematological irAEs caused by checkpoint inhibitors. This study delineates the overview of hematological irAEs, and provides practical treatment suggestions, in particular addressing the issue of rechallenge.

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Severe complicated neutropenia in two patients with metastatic non-small-cell lung cancer treated with nivolumab

Cited by 41 publications

References 11 publications

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

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

Do checkpoint inhibitors compromise the cancer patients’ Immunity and Increase the Vulnerability to COVID-19 Infection?

Clinical diagnosis and treatment recommendations for immune checkpoint inhibitor‐related hematological adverse events

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