Cytokine Release Syndrome Following BNT162b2 Vaccination in a Colorectal Cancer Patient on Anti-PD-1 Therapy
Jun 02, 2021 10:02
CST Updated
Jun 15, 09:56
Pfizer
Pharmaceutical R&D Developer
BioNTech
Developer of Novel Biologics
The Francis Crick Institute
The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the mechanisms of biological science.
Currently, global coronavirus disease 2019 (COVID-19) vaccination programs prioritize cancer patients, including the use of mRNA vaccines. Cytokine release syndrome (CRS) has not yet been reported following mRNA vaccination; it is an extremely rare immune-related adverse event associated with immune checkpoint inhibitors. Lewis Au et al. published an article titled "Cytokine Release Syndrome Following BNT162b2 Vaccination in a Patient with Colorectal Cancer" in Nature Medicine.In this study, the authors reported a case of a patient with colorectal cancer on long-term anti-PD-1 monotherapy, who was vaccinated,`Pfizer`- A case of CRS occurring 5 days after administration of the BioNTech COVID-19 mRNA vaccine BNT162b2 (tozinameran).Elevated inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10), and response to steroids are evidence of CRS. In this case, vaccination and# DiagnosisThe close temporal correlation of CRS suggests that it is a vaccine-related adverse event, with anti-PD-1 blockade as a potential contributor. Overall, further prospective pharmacovigilance data are needed in cancer patients; however, in this population, the benefit-risk profile still strongly supports COVID-19 vaccination.
Image source: https://www.nature.com/articles/s41591-021-01387-6
CRS/cytokine storm is a systemic inflammatory response characterized by excessive cytokine release (i.e., elevated levels of IFN-γ, IL-6, IL-10, and IL-2R). CRS may occur following infection (including COVID-19) or due to iatrogenic causes, most notably chimeric antigen receptor T-cell (CAR-T) therapy, and less commonly cytotoxic chemotherapy orStem cellsTransplantation. Extremely rarely, it occurs following treatment with immune checkpoint inhibitors (ICIs); herein, the authors report a case of cytokine release syndrome (CRS) following vaccination with the COVID-19 mRNA vaccine BNT162b2 (tozinameran).
A 58-year-old male initiated anti-PD-1 monotherapy (an ongoing interventionalClinical Trialexperimental ICI; NCT02715284), for the treatment of mismatch repair-deficient colorectal cancer (MMRd CRC) with metastases to the mesentery and rectus muscle. Two months after treatment initiation, he experienced a neurological immune-related adverse event (irAE), which worsened against a background of idiopathic spinocerebellar ataxia (Grade 1 to 2, with MRI changes in the pons, medulla, and cerebellum). ICI was suspended, and he was started on prednisolone at 1 mg/kg (tapered after 1 month), with ataxia returning to Grade 1 (baseline). Anti-PD-1 therapy was resumed in June 2019, according to solidTumorPer immune-related response criteria, disease was stable. In March 2020 (13 months after initiation of ICI), he developed an endocrine irAE (Grade 1 hypocortisolism secondary to ACTH deficiency) and was started on physiologic corticosteroid replacement (prednisolone, 3 mg daily). Disease control was maintained; the last oral ICI dose was administered in December 2020, 27 days prior to BNT162b2.
During cancer-associated CRSDiagnosisClinical Course to Inflammatory Markers
Image source: https://www.nature.com/articles/s41591-021-01387-6
Given that cancer patients were excluded from SARS-CoV-2 vaccine trials and are currently prioritized in global COVID-19 vaccination programs, this case underscores the need for prospective pharmacovigilance regarding the safety of COVID-19 vaccines in cancer patients. To date, prospective data have not demonstrated additional safety concerns associated with BNT162b2 in cancer patients overall (n = 151) or specifically in those receiving immune checkpoint inhibitor (ICI) therapy (n = 170).Current evidence-based recommendations regarding the timing of COVID-19 vaccination indicate that, for cancer patients receiving systemic anticancer therapy, including immune checkpoint inhibitors (ICI), cytotoxic chemotherapy, and hormone therapy, vaccination should be avoided within 48 to 72 hours following the administration of investigational products to minimize the misattribution of adverse event causes.Overall, given that the CRS in this case is an isolated report and cancer patients are generally more susceptible to COVID-19 infection, the benefit-risk profile of COVID-19 vaccination still strongly supports vaccination in this population. Prioritizing cancer patients during vaccine rollout is crucial.（Bioon Bioon.com）
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