Are patients on pembrolizumab (pembrolizumab) considered immunocompromised?

Patients on Pembrolizumab Are Considered Immunocompromised

Yes, patients receiving pembrolizumab should be considered immunocompromised due to the drug's mechanism of action and risk of opportunistic infections. 1

Mechanism and Immunocompromised Status

Pembrolizumab is a humanized IgG4 monoclonal antibody that targets the programmed cell death protein-1 (PD-1) receptor, blocking its interaction with PD-L1 and PD-L2 ligands. This blockade:

• Disrupts normal immune regulatory mechanisms
• Enhances T-cell mediated cytotoxicity against tumor cells
• Can simultaneously disrupt immune control of specific opportunistic infections 1

The 2019 Journal for ImmunoTherapy of Cancer guidelines specifically address this question, noting that the blockade of the PD-1/PD-L1 axis may disrupt immune control of opportunistic infections such as tuberculosis, indicating these patients should be considered immunocompromised 1.

Evidence of Immunocompromised Status

Several clinical observations support classifying pembrolizumab patients as immunocompromised:

1. Reactivation of latent infections: Cases of latent tuberculosis reactivation have been documented in patients receiving PD-1/PD-L1 inhibitors like pembrolizumab 1

2. Immune-related adverse events requiring immunosuppression: Many patients develop immune-related adverse events that require treatment with high-dose corticosteroids or other immunosuppressive medications (e.g., TNF-α inhibitors, mycophenolate mofetil), further compromising immune function 1

3. Opportunistic infections: The guidelines note specific concerns about opportunistic infections in patients receiving checkpoint inhibitors 1

Clinical Implications

The immunocompromised status of patients on pembrolizumab has several important clinical implications:

• Screening for latent infections: Consider screening for latent tuberculosis and other opportunistic infections before initiating therapy 1

• Monitoring for infection: Maintain vigilance for signs of infection during treatment

• Vaccination considerations: Live vaccines should generally be avoided in these patients

• Management of immune-related adverse events: Prompt recognition and treatment of immune-related adverse events is essential, as these often require immunosuppressive therapy that further compromises immune function 1

Common Immune-Related Adverse Events

Pembrolizumab can cause various immune-related adverse events that may require immunosuppressive treatment:

• Colitis
• Hepatitis
• Pneumonitis
• Endocrinopathies (thyroiditis, type 1 diabetes) 2
• Rare but serious hematologic complications 3

Pitfalls to Avoid

1. Underestimating infection risk: Don't assume that immune activation against tumors means better protection against pathogens - the opposite may be true for certain infections 1

2. Delayed recognition of immune-related adverse events: These can mimic other conditions and require prompt immunosuppressive treatment

3. Inappropriate vaccination: Live vaccines should be avoided due to the immunocompromised status

4. Failure to screen for latent infections: Consider screening for tuberculosis and other latent infections before starting therapy 1

In conclusion, while pembrolizumab enhances anti-tumor immune responses, it simultaneously disrupts normal immune regulatory mechanisms, placing patients at risk for opportunistic infections and immune-related adverse events. Therefore, patients on pembrolizumab should be considered immunocompromised and managed accordingly.