Managing Side Effects of Pembrolizumab: A Practical Guide

Pembrolizumab works by activating the immune system - and a more active immune system can sometimes attack healthy tissue. These effects are called immune-related adverse events (irAEs). Understanding what to expect, how to recognise early warning signs, and when to contact your clinical team is an important part of being on treatment.

Common side effects

The most frequently reported side effects with pembrolizumab are fatigue, skin rash, diarrhoea, and joint pain. These are generally mild and manageable for most patients. Fatigue is particularly common - it often peaks in the days after treatment and gradually improves before the next cycle. Pacing activity, maintaining gentle movement where possible, and prioritising rest can all help manage treatment-related fatigue.

Skin reactions ranging from mild rash to more significant irritation are reported in a meaningful proportion of patients. Any new rash that develops during treatment should be reported to your clinical team, as it may be an early sign of an immune skin reaction that warrants closer monitoring or management.

Immune-related adverse events (irAEs)

irAEs can affect almost any organ. The most commonly affected systems are:

• Thyroid: Both underactive (hypothyroidism) and overactive (hyperthyroidism) thyroid conditions are common, often picked up on routine blood tests before symptoms develop. Most cases are managed with thyroid hormone replacement and do not require stopping pembrolizumab.
• Skin: Rashes, vitiligo (loss of skin pigmentation, particularly common in melanoma patients), and, rarely, more severe skin reactions.
• Liver (hepatitis): Liver inflammation is detected through abnormal liver function tests. Most cases resolve with steroids.
• Lungs (pneumonitis): Inflammation of the lung tissue, presenting as breathlessness or a new cough. Requires prompt assessment and usually treatment with steroids.
• Bowel (colitis): Inflammation causing diarrhoea, which can become severe if not managed early.

Symptoms that need prompt attention

Some irAEs can escalate quickly if not treated. Contact your clinical team promptly if you experience any of the following:

• Severe or persistent diarrhoea (more than three loose stools per day, or any blood in stool)
• New breathlessness, a persistent cough, or chest pain
• Significant new skin reaction affecting large areas of the body
• Yellowing of the skin or whites of the eyes (jaundice)
• Severe headache, confusion, or new neurological symptoms
• Significant new joint pain or muscle weakness

These symptoms do not necessarily mean pembrolizumab needs to be stopped permanently - but they do need same-day assessment. Early treatment of irAEs significantly improves outcomes.

Monitoring and safety oversight

Regular blood tests - including full blood count, liver function, thyroid function, kidney function, and glucose - are standard at defined intervals during pembrolizumab treatment. These tests often detect subclinical problems before they cause symptoms. In our home-based model, baseline observations are taken at every visit, and the clinical team is available between appointments for any concerns. Remote check-ins between cycles are built into the programme.

The goal of monitoring is to catch problems early, when they are most manageable - and to allow treatment to continue safely for as long as it is beneficial.