Cytokine release syndrome as an important differential diagnosis of severe skin toxicity with organ damage during switch from immunotherapy to targeted therapy in metastatic melanoma

Dimitriou, Florentia; Mangana, Joanna; Micaletto, Sara; Braun, Ralph; Dummer, Reinhard

doi:10.1097/cmr.0000000000000544

Cited by 4 publications

(2 citation statements)

References 6 publications

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“…The pathophysiology of CRS among patients with melanoma who are sequentially treated with immunotherapies followed by targeted therapies remains unclear but has been recently hypothesized to be a result of simultaneous exposure to immune-checkpoint and MAPK inhibition due to the long half-life of immune-checkpoint inhibitors, resulting in T-cell activation and release of multiple cytokines including IL-6 [2,4]. IL-6 causes a positive feedback loop and at high levels initiates a proinflammatory cascade through the trans-signaling pathway [4][5][6]. Notably, our patient as well as both published cases of this were exposed to T-cell stimulating therapies prior to initiation of MEK and BRAF inhibition (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of Cytokine Release Syndrome with IL-6 Blockade in a Patient Transitioning from Immune-Checkpoint to MEK/BRAF Inhibition: A Case Report and Review of Literature

et al. 2020

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There are now multiple targeted and immunotherapies available for the treatment of metastatic melanoma. Although these agents have dramatically improved the survival of patients, the appropriate sequencing and the safety during the transition between these drugs remains unknown. Recently two cases of cytokine release syndrome (CRS) following transition from immune-checkpoint inhibitors to BRAF and MEK inhibitors (BRAFi/MEKi) in patients with metastatic melanoma have been reported. CRS is a systemic cytokinedriven inflammatory reaction, previously well reported in chimeric antigen receptor T-cell therapies for hematologic malignancies. Here, we report a third case in which severe CRS resistant to glucocorticoid therapy following transition to a MEKi/BRAFi was treated successfully with tocilizumab, an interleukin-6 (IL-6) inhibitor. CRS should be on the differential diagnosis of immune-related adverse events of immunotherapies or targeted cancer therapies for metastatic melanoma, and clinicians in multiple disciplines should be aware of this rare complication and the potential benefits of IL-6 blockade.

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Section: Discussionmentioning

confidence: 99%

Successful Treatment of Cytokine Release Syndrome with IL-6 Blockade in a Patient Transitioning from Immune-Checkpoint to MEK/BRAF Inhibition: A Case Report and Review of Literature

et al. 2020

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“…Thus, the benefits associated with ICIs come at the cost of irAEs, and the increased efficacy is usually accompanied by irAEs. Unlike typical chemotherapy-related toxicity, it can be considered of off-target effects of an over-activated immune system (F et al, 2019), immune-related adverse events often manifest as immune-associated colitis ( Liu Z. et al, 2021 ), diarrhea ( Kelly-Goss et al, 2022 ), rash ( Dimitriou et al, 2019 ), arthritis ( Kostine et al, 2021 ) and so on ( Stanley et al, 2016 ). Higher abundance of gut microbiota has been observed in patients experiencing mild diarrhea compared to those with severe diarrhea, suggesting that enrichment of the gut microbiota is important for the prevention of irAEs.…”

Section: Gut Microbiota In Immune-related Toxicitymentioning

confidence: 99%

Potential role of gut microbes in the efficacy and toxicity of immune checkpoints inhibitors

Cheng

et al. 2023

Front. Pharmacol.

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In recent years, Immune checkpoint inhibitors have been extensively used in the treatment of a variety of cancers. However, the response rates ranging from 13% to 69% depending on the tumor type and the emergence of immune-related adverse events have posed significant challenges for clinical treatment. As a key environmental factor, gut microbes have a variety of important physiological functions such as regulating intestinal nutrient metabolism, promoting intestinal mucosal renewal, and maintaining intestinal mucosal immune activity. A growing number of studies have revealed that gut microbes further influence the anticancer effects of tumor patients through modulation of the efficacy and toxicity of immune checkpoint inhibitors. Currently, faecal microbiota transplantation (FMT) have been developed relatively mature and suggested as an important regulator in order to enhance the efficacy of treatment. This review is dedicated to exploring the impact of differences in flora composition on the efficacy and toxicity of immune checkpoint inhibitors as well as to summarizing the current progress of FMT.

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Clinical features of acute kidney injury in patients receiving dabrafenib and trametinib

Seethapathy

Lee

Strohbehn

et al. 2020

Nephrology Dialysis Transplantation

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Objectives To characterize the incidence, risk factors, and clinical features of acute kidney injury (AKI) in patients receiving dabrafenib and trametinib. Methods We performed a retrospective cohort study examining the kidney outcomes of patients in a large healthcare system who received dabrafenib/trametinib between 2010 and 2019. The primary outcome was AKI, defined as a 1.5-fold increase in serum creatinine from baseline within a 12-month study period. AKI severity and etiology was determined for each case by chart review. Logistic regression was used to evaluate baseline predictors of AKI. Results 199 patients who received dabrafenib in our healthcare system from 2010-2019 were included in the analysis. Forty-two patients (21%) experienced AKI within 12 months; 10 patients (5% of total cohort, 24% of AKI) experienced AKI occurring during a dabrafenib/trametinib-induced febrile syndrome characterized by fever, chills, gastrointestinal symptoms, and elevated liver enzymes. Pre-existing liver disease was the only significant predictor of AKI in the cohort. One patient had biopsy-proven granulomatous acute interstitial nephritis that resolved with corticosteroids. Conclusions Oncologists and nephrologists should be aware that AKI is common after dabrafenib/trametinib and a substantial number of cases occur in the setting of treatment-induced pyrexia.

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Cytokine release syndrome as an important differential diagnosis of severe skin toxicity with organ damage during switch from immunotherapy to targeted therapy in metastatic melanoma

Cited by 4 publications

References 6 publications

Successful Treatment of Cytokine Release Syndrome with IL-6 Blockade in a Patient Transitioning from Immune-Checkpoint to MEK/BRAF Inhibition: A Case Report and Review of Literature

Successful Treatment of Cytokine Release Syndrome with IL-6 Blockade in a Patient Transitioning from Immune-Checkpoint to MEK/BRAF Inhibition: A Case Report and Review of Literature

Potential role of gut microbes in the efficacy and toxicity of immune checkpoints inhibitors

Clinical features of acute kidney injury in patients receiving dabrafenib and trametinib

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