Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2

AbstractPatients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)—the Pfizer-BioNTech mRNA COVID-19 vaccine—in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit–risk profile remains strongly in favor of COVID-19 vaccination in this population.

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Delayed cytokine release syndrome after neoadjuvant nivolumab: a case report and literature review

Immunotherapy ◽

10.2217/imt-2020-0329 ◽

2021 ◽

Author(s):

Aaron T Ciner ◽

Howard S Hochster ◽

David A August ◽

Darren R Carpizo ◽

Kristen R Spencer

Keyword(s):

Adverse Event ◽

Checkpoint Inhibitors ◽

Corticosteroid Treatment ◽

Hemodynamic Instability ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Related Adverse Event ◽

Neoadjuvant Immunotherapy ◽

Appropriate Treatment ◽

High Index Of Suspicion

Aim: Cytokine release syndrome (CRS) is an infrequently described immune-related adverse event of checkpoint inhibitors (CPI). CPI-induced CRS typically presents with fevers, hemodynamic instability and organ dysfunction within 2 weeks of the last treatment cycle. Case study: We report an unusual case of delayed and severe CRS occurring postoperatively in a patient with hepatic-limited metastatic colorectal cancer who received neoadjuvant immunotherapy. After a negative workup for alternative causes, he received prolonged corticosteroid treatment with symptom resolution. Conclusion: CPI-induced CRS can mimic sepsis and clinicians should maintain a high-index of suspicion to diagnose this immune-related adverse event early and initiate appropriate treatment. As use of perioperative immunotherapy increases, the potential role of surgery to trigger CRS in this case warrants further investigation.

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Bioactive Lipid (BAL)-Based Therapeutic Approach to Cancer That Enhances Antitumor Action and Ameliorates Cytokine Release Syndrome of Immune Checkpoint Inhibitors

Molecular Biochemical Aspects of Cancer ◽

10.1007/978-1-0716-0741-1_6 ◽

2020 ◽

pp. 207-235

Author(s):

Undurti N. Das

Keyword(s):

Immune Checkpoint ◽

Therapeutic Approach ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Antitumor Action ◽

Cytokine Release ◽

Cytokine Release Syndrome

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Case Report: A Case of Trimethoprim/Sulfamethoxazole-Triggered Hypotensive Shock: Cytokine Release Syndrome Related to Immune Checkpoint Inhibitors and Drug-Induced Hypersensitivity Syndrome

Frontiers in Oncology ◽

10.3389/fonc.2021.681997 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tetsuya Urasaki ◽

Makiko Ono ◽

Toshiaki Mochizuki ◽

Koichi Takeda ◽

Aya Nishizawa ◽

...

Keyword(s):

Immune Checkpoint ◽

Interstitial Pneumonitis ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Hypersensitivity Syndrome ◽

High Dose ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Drug Induced ◽

Prophylactic Administration

Currently, only a few reports exist on the cytokine release syndrome (CRS) as one of the severe immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs). Notably, it is very rare that grade 4 CRS related to ICI therapy overlaps with the drug-induced hypersensitivity syndrome (DiHS). A 46-year old woman with metastatic kidney cancer had grade 3 interstitial pneumonitis induced by four cycles of combination therapy of anti-programmed death-1 and anti-cytotoxic T lymphocyte-4 antibodies after right cytoreductive nephrectomy. Prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) was started concomitantly with prednisolone therapy to treat the interstitial pneumonitis. She developed hypotensive shock when reducing the dosage of prednisolone, and required intubation and ventilation using vasopressors at the intensive care unit. She subsequently exhibited prominent leukocytosis and an increased level of C-reactive protein, suggesting markedly increased cytokine levels. Interestingly, facial edema and erythema increased in association with pyrexia, leukocytosis, liver dysfunction, and renal failure, suggesting that she developed DiHS. She received hemodialysis three times, a plasma exchange, and anti-interleukin-6 therapy to treat severe renal dysfunction, a thrombotic thrombocytopenic purpura-suspected condition, and possible grade 4 CRS, respectively. Although these therapies did not elicit sufficient effects, high-dose administration of intravenous immunoglobulin was successful. With steroid mini-pulse therapy and the subsequent administration of prednisolone, she recovered successfully. To the best of our knowledge, this is the first report that ICIs and TMP/SMX can induce hypotensive shock accompanied with CRS and DiHS during immunosuppressive therapy for an irAE. Importantly, the prophylactic administration of TMP/SMX should be performed cautiously to avoid severe drug reactions such as CRS or DiHS.

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Evaluation and clinical impact of a pharmacist-led, interdisciplinary service focusing on education, monitoring and toxicity management of immune checkpoint inhibitors

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211061133 ◽

2021 ◽

pp. 107815522110611

Author(s):

Glenn Myers ◽

Jonathan Stevens ◽

Andrew Flewelling ◽

Jacqueline Richard ◽

Meagan London

Keyword(s):

Adverse Event ◽

Patient Outcomes ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Study Cohort ◽

Control Cohort ◽

Related Adverse Event

Introduction Immune-related adverse events are complications of immune checkpoint inhibitors which require robust patient education and proactive follow-up to ensure timely identification and management. Oncology pharmacist practice models with other anticancer modalities have been well documented, but there is limited evidence assessing the spectrum of pharmacist interventions in patients receiving immune checkpoint inhibitor(s) and the impact of these interventions on patient outcomes. Methods Patients initiated on immune checkpoint inhibitor(s) from 1 January 2016 to 31 August 2019 were included for data collection and analysis. Part 1 featured an intensive pharmacist follow-up cohort (study cohort) and summarized pharmacist interventions. Part 2 compared patient outcomes between the study cohort and a standard of care cohort (control cohort) from a different oncology centre. Patient outcomes included emergency department visits not resulting in admission, hospitalizations due to immune-related adverse event(s), immune checkpoint inhibitor cycles received, treatment discontinuation due to immune-related adverse event(s), completion of finite programmed death-1/death-1 ligand treatment course and completion of ipilimumab. Clinical outcomes were compared using a retrospective, matched cohort design based on age, cancer diagnosis and immune checkpoint inhibitor(s). Results A total of 143 patients were included in Part 1 encompassing 1664 pharmacist recommendations across 11 categories. The matched cohort yielded 92 matches (n = 184) with a higher odds of immune checkpoint inhibitor discontinuation due to immune-related adverse event(s) in the control cohort (odds ratio (OR) (95% confidence interval (CI)) = 5.5 (1.2−24.8); p = 0.022). Conclusion Intensive immune-related adverse event education, proactive follow-up and immune-related adverse event management by pharmacists result in clinically meaningful interventions which correlate to improved patient outcomes, namely lower odds of treatment discontinuation due to immune-related adverse event(s).

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