From the Guidelines
Pembrolizumab can cause immune-related adverse events including fever, vomiting, and diarrhea that require prompt management, and the most recent guidelines recommend a step-wise approach to managing these symptoms, starting with supportive care for mild symptoms and escalating to corticosteroids and potentially infliximab for more severe symptoms 1.
Management of Immune-Related Adverse Events
The management of immune-related adverse events (irAEs) associated with pembrolizumab is crucial to prevent long-term damage and improve patient outcomes. According to the most recent guidelines, the approach to managing irAEs should be based on the severity of the symptoms.
- For mild symptoms (grade 1), supportive care with antipyretics like acetaminophen for fever, antiemetics such as ondansetron for vomiting, and loperamide for mild diarrhea may be sufficient while continuing pembrolizumab 1.
- For moderate symptoms (grade 2), especially diarrhea with 4-6 stools per day, pembrolizumab should be withheld and prednisone 1 mg/kg/day started 1.
- For severe symptoms (grade 3-4), with diarrhea exceeding 7 stools daily or requiring hospitalization, permanently discontinue pembrolizumab and initiate high-dose corticosteroids (methylprednisolone 1-2 mg/kg/day) 1.
Importance of Early Intervention
Early intervention is crucial in managing irAEs, as these side effects can become life-threatening if not properly managed. It is essential to rule out infectious causes with stool studies before attributing symptoms solely to immune-related toxicity 1.
Pathogenesis of Immune-Related Adverse Events
The pathogenesis of immune-related adverse events is not fully understood but is thought to be related to the removal of inhibitory signals on T-cells, potentially causing them to attack healthy tissues, including the gastrointestinal tract 1.
From the FDA Drug Label
Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). Other clinically important adverse reactions occurring in patients receiving KEYTRUDA were fatigue (25%), diarrhea (14%), asthenia (11%) and pyrexia (11%) Other clinically important adverse reactions occurring in ≥10% of patients receiving KEYTRUDA were diarrhea (26%), nausea (21%), and pruritus (17%)
The adverse reactions of fever, vomiting, and diarrhea with pembrolizumab are:
- Diarrhea occurred in 14% of patients and led to interruption of KEYTRUDA in 1% of patients.
- Vomiting occurred in 13% of patients.
- Fever (pyrexia) occurred in 11% of patients. These adverse reactions are common with pembrolizumab treatment 2, 2.
From the Research
Symptoms Associated with Pembrolizumab
- Fever, vomiting, and diarrhea are potential side effects of pembrolizumab, as reported in various studies 3, 4.
- These symptoms can be indicative of immune-related adverse events (irAEs), which are a known complication of immune checkpoint inhibitors like pembrolizumab 3.
Specific Cases and Studies
- A case study published in the Clinical Journal of Gastroenterology reported an 82-year-old man who developed diarrhea, melena, fever, and hyperamylasemia after receiving pembrolizumab for lung cancer, which was diagnosed as colitis and pancreatitis due to autoimmune side effects of pembrolizumab 3.
- Another study published in the World Journal of Clinical Cases reported a case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment, but responded to infliximab 4.
Management of Symptoms
- The management of nausea and vomiting, which can be associated with pembrolizumab treatment, involves a 5-step approach, including defining the symptoms, determining their duration, considering medication or toxin adverse effects, formulating a differential diagnosis, and directing treatment based on the underlying cause 5.
- A study published in the American Family Physician recommended that acute nausea and vomiting be treated symptomatically, while chronic symptoms require a more extensive evaluation to identify the underlying cause 6.