Nivolumab-Induced Cytokine-Release Syndrome in Relapsed/Refractory Hodgkin’S Lymphoma: A Case Report and Literature Review

Zhao, Lingdi; Yang, Yue; Li, Wei; Li, Tiepeng; Gao, Quanli

doi:10.2217/imt-2018-0025

Cited by 22 publications

(17 citation statements)

References 28 publications

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“…However, expanding indications and advancing effectiveness of ICIs would increase the incidence of this disease in cancer patients. Although our current case showed significantly high blood concentration of IL-1β, IL-6, TNFα, and IFNγ when compared with previous reports of CRS [18–20], we did not use the inhibitory agents for inflammatory cytokines in this case because these were not yet recommended in the actual clinical setting at that time. However, a study reported that administration of anti-IL-6 receptor monoclonal antibody (tocilizumab) was useful for treatment of CRS [12].…”

Section: Resultscontrasting

confidence: 58%

Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report

Honjo¹,

Kubo²,

Sugaya³

et al. 2019

j. immunotherapy cancer

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Background Immune checkpoint inhibitors (ICIs) have provided more options in the treatment of lung cancer. However, ICIs can cause several unfavorable reactions generally referred to as immune-related adverse effects. Case presentation In this report, we present the case of a 52-year-old woman with successful regression of pleomorphic carcinoma of the lung following nivolumab therapy. She developed purpura fulminans (PF) ultimately resulting in amputation of both lower extremities. Blood tests revealed thrombocytopenia with increased serum soluble IL-2 receptor, ferritin, and triglyceride levels suggesting hemophagocytic lymphohistiocytosis (HLH). In addition, serum A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 activity was decreased, suggesting thrombotic thrombocytopenic purpura (TTP). Further detailed analysis revealed severe hypercytokinemia including increased levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, and G-CSF. Conclusion The severe systemic inflammatory reaction and impaired peripheral circulation in this patient was attributed to excessive immunological effect induced by nivolumab resulting in cytokine release syndrome (CRS). This is the first report of a patient with multiple pathological conditions including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Further accumulating thoroughly investigated cases would lead to better understanding of the disease and development of reliable cancer immunotherapy.

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Section: Resultscontrasting

confidence: 58%

Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report

Honjo¹,

Kubo²,

Sugaya³

et al. 2019

j. immunotherapy cancer

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“…Regardless of cancer type, ICI-related CRS safety reports were more numerous on anti-PD-1/PD-L1 antibodies, in line with the single case reports of CRS developed on either nivolumab or pembrolizumab (Foran et al, 2017;Rassy et al, 2017;Rotz et al, 2017;Zhao et al, 2018;Dimitriou et al, 2019;Honjo et al, 2019;Kogure et al, 2019;Oda et al, 2019). Moreover, a recent review of the largest clinical trials of ICIs (Michot et al, 2019), found that the frequency of hematological irAEs of all grades (including CRS), was higher with anti-PD-1 (4.1%) and anti-PD-L1 (4.7%) than with anti-CTLA-4 agents (0.5%, P < 0.0001).…”

Section: Discussionsupporting

confidence: 54%

“…Despite the strict parallelism between ICI mechanism of action and CRS pathophysiologic mechanism, to date, only a few case reports have documented the association of ICIs as pharmacological triggers of CRS in cancer patients (Foran et al, 2017;Rassy et al, 2017;Rotz et al, 2017;Zhao et al, 2018;Dimitriou et al, 2019;Honjo et al, 2019;Kogure et al, 2019;Oda et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database

et al. 2020

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Immune checkpoint inhibitors (ICIs) have proven effective in the treatment of numerous cancers; however, they have been associated with immune-related adverse events (irAEs), among which cytokine release syndrome (CRS) has been reported in a few case reports. To describe the burden of ICI-related CRS and raise awareness of CRS as irAE, we queried VigiBase, the World Health Organization global database of spontaneously reported suspected adverse drug reactions (ADRs), and retrieved safety reports of suspected CRS associated with ICIs, gathered in the database through January 12 th 2020. We assessed ICI-related CRS safety reports in terms of geographical and temporal patterns of reporting, patient demographics and clinical features, treatment characteristics, CRS clinical presentation, timing, seriousness, and outcome. We retrieved 58 cases of whom 43 (74%) reported CRS with anti-programmed death-1/antiprogrammed death-ligand 1 agents. Melanoma (n=17, 29%) and hematologic malignancies (n=16, 28%) were the most common underlying cancers. ICIs were the solely suspected drugs in 37 (64%) cases. Typical signs and symptoms of CRS were reported in 25 (43%) patients. ICI-related CRS developed a median of 4 weeks after ICI initiation (IQR 1-18 weeks, n=9, 16%). Besides two fatal cases, CRS recovered/was recovering at the time of reporting in 35 (60%) cases. We observed differences in the geographical pattern of ICI-related CRS reporting, with a high proportion of ICI-related CRS cases in Australia and North America (0.14 and 0.10% respectively). Due to ICI expanding indications, clinicians should be aware that ICIs could contribute to CRS onset in cancer patients as pharmacological triggers.

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“…Pharmacology, pharmacokinetics, clinical efficacy, safety, and role of tocilizumab in rheumatoid arthritis (RA) are well-established [58] and possibly due also to its effect on the AKT/mTOR pathway [59]. Tocilizumab has also been approved for the treatment of the cytokine storm associated with cancer immunotherapy [60] or, more often, with CAR-T therapy [61,62]. This MoAb does not have direct antiviral effects, but effectively contrasts the massive cytokine release syndrome displayed in severe COVID-19 by antagonizing the binding of IL-6, one of the cytokines most involved in this process, to its receptor [58].…”

Section: Immunomodulatory Medications Tocilizumabmentioning

confidence: 99%

Drug repurposing against COVID-19: focus on anticancer agents

Ciliberto

Mancini

Paggi³

2020

J Exp Clin Cancer Res

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Background: The very limited time allowed to face the COVID-19 pandemic poses a pressing challenge to find proper therapeutic approaches. However, synthesis and full investigation from preclinical studies to phase III trials of new medications is a time-consuming procedure, and not viable in a global emergency, such as the one we are facing. Main Body: Drug repurposing/repositioning, a strategy effectively employed in cancer treatment, can represent a valid alternative. Most drugs considered for repurposing/repositioning in the therapy of the COVID-19 outbreak are commercially available and their dosage and toxicity in humans is well known, due to years (or even decades) of clinical use. This can allow their fast-track evaluation in phase II-III clinical trials, or even within straightforward compassionate use. Several drugs being re-considered for COVID-19 therapy are or have been used in cancer therapy. Indeed, virusinfected cells are pushed to enhance the synthesis of nucleic acids, protein and lipid synthesis and boost their energy metabolism, in order to comply to the "viral program". Indeed, the same features are seen in cancer cells, making it likely that drugs interfering with specific cancer cell pathways may be effective as well in defeating viral replication. Short Conclusion: To our knowledge, cancer drugs potentially suitable for facing SARS-CoV-2 infection have not been carefully reviewed. We present here a comprehensive analysis of available information on potential candidate cancer drugs that can be repurposed for the treatment of COIVD-19.

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Nivolumab-Induced Cytokine-Release Syndrome in Relapsed/Refractory Hodgkin’S Lymphoma: A Case Report and Literature Review

Cited by 22 publications

References 28 publications

Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report

Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database

Drug repurposing against COVID-19: focus on anticancer agents

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