Can Pembrolizumab (pembrolizumab) cause fever (pyrexia)?

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Last updated: February 27, 2025View editorial policy

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From the Guidelines

Pembrolizumab can cause fever as a side effect, with the most recent and highest quality study indicating that fever is one of the common adverse events associated with pembrolizumab 1. The fever typically develops within the first few weeks of treatment but can occur at any time during therapy. It is often mild to moderate in severity and may be accompanied by other flu-like symptoms such as chills, fatigue, and body aches. The fever results from pembrolizumab's mechanism of action as an immune checkpoint inhibitor that enhances T-cell activation, leading to increased production of inflammatory cytokines. Some key points to consider when managing fever in patients receiving pembrolizumab include:

  • For mild fever (less than 38.5°C or 101.3°F), acetaminophen can be used for symptom management, and patients can generally continue pembrolizumab treatment.
  • Persistent or high-grade fever should prompt medical evaluation to rule out infection or other immune-related adverse events that may require corticosteroid treatment or temporary discontinuation of pembrolizumab.
  • Patients should monitor their temperature regularly during treatment and report persistent or severe fever to their healthcare provider immediately. The most common adverse events from pembrolizumab are fatigue, pruritus, diarrhea, anorexia, constipation, nausea, rash, fever, cough, dyspnea, and musculoskeletal pain, as reported in the study 1. Additionally, pembrolizumab may be associated with immune-mediated side effects, which include colitis, hepatitis, endocrinopathies, pneumonitis, or nephritis, as noted in the study 1. It is essential to weigh the benefits and risks of pembrolizumab treatment and to closely monitor patients for any adverse events, including fever. In the context of real-life clinical medicine, it is crucial to prioritize the patient's safety and well-being, and to make decisions based on the most recent and highest quality evidence available, such as the study published in 2023 1.

From the FDA Drug Label

Table 20: Adverse Reactions (≥10%) in Patients with cHL who Received KEYTRUDA in KEYNOTE-087 ... General Fatigue† 26 10 Pyrexia 24 1.0

Table 22: Adverse Reactions (≥10%) in Patients with PMBCL who Received KEYTRUDA in KEYNOTE-170 ... General Pyrexia 28 0

Table 24: Adverse Reactions ≥20% (All Grades) in Patients Treated with KEYTRUDA in Combination with Enfortumab Vedotin in KEYNOTE-A39 ... General disorders and administration site conditions Pyrexia 2 0

Table 53: Adverse Reactions Occurring in ≥20% of Patients Receiving KEYTRUDA in KEYNOTE-522 ... General Pyrexia 28 1.3

Yes, Pembrolizumab (pembrolizumab) can cause fever (pyrexia), as it is listed as an adverse reaction in the provided drug labels 2 and 2. The incidence of pyrexia varies across different studies, but it is reported in multiple tables, indicating that it is a potential side effect of the medication.

From the Research

Pembrolizumab and Fever (Pyrexia)

  • Pembrolizumab has been associated with various immune-related adverse events, including fever (pyrexia) 3, 4.
  • A case study reported a 70-year-old man who presented with breathlessness, cough, and fever while receiving pembrolizumab for melanoma 3.
  • Another study reported an 82-year-old man who developed diarrhea, melena, and fever after six doses of pembrolizumab for lung cancer, and was diagnosed with colitis and pancreatitis 4.
  • These cases suggest that pembrolizumab can cause fever (pyrexia) as part of its immune-related adverse events.

Immune-Related Adverse Events

  • Pembrolizumab has been associated with a range of immune-related adverse events, including pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes 5.
  • Elderly patients on pembrolizumab therapy require close monitoring for immune-related adverse events, which can present atypically or without symptoms and may be fatal 6.
  • The management of immune-related adverse events during pembrolizumab therapy is crucial, and may involve the use of high-dose cortisone therapy, thyroid hormone substitution, and other treatments 5, 6.

Professional Medical Disclaimer

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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