What is the appropriate management for pembrolizumab (pembrolizumab, an anti-PD-1 antibody)-induced cytokine release syndrome (CRS) presenting with rash, acute transverse myelitis (ATM), and inflammatory arthritis?

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Last updated: June 22, 2025View editorial policy

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From the Research

Management of pembrolizumab-induced cytokine release syndrome (CRS) with rash, acute transverse myelitis, and inflammatory arthritis requires immediate discontinuation of pembrolizumab and initiation of high-dose corticosteroids, as supported by the most recent study 1. The treatment should start with methylprednisolone 1-2 mg/kg/day IV or equivalent, typically for 3-5 days, followed by oral prednisone 1 mg/kg/day with a gradual taper over 4-6 weeks based on clinical response. Some key points to consider in the management of CRS include:

  • For severe or steroid-refractory cases, consider adding tocilizumab (8 mg/kg IV, maximum 800 mg) as it specifically blocks IL-6, a key cytokine in CRS pathophysiology, as seen in a case report 1.
  • The neurologic manifestation of transverse myelitis requires urgent neurological consultation and may necessitate more aggressive immunosuppression, potentially including plasma exchange or intravenous immunoglobulin (IVIG 2 g/kg divided over 2-5 days), as reported in a study on longitudinal extensive transverse myelitis 2.
  • Supportive care is essential, including antipyretics, IV fluids, and close monitoring of vital signs and organ function.
  • The inflammatory arthritis component may require additional NSAIDs or disease-modifying antirheumatic drugs if persistent after steroid treatment, as noted in a case of pembrolizumab-induced inflammatory arthritis 3. This comprehensive approach targets the underlying immune hyperactivation causing these immune-related adverse events, as pembrolizumab's blockade of PD-1 can lead to dysregulated T-cell activation and inflammatory cytokine release affecting multiple organ systems, as highlighted in a case report of CRS induced by pembrolizumab 4.

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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