How to manage patients on beta blockers (beta-adrenergic blocking agents) and immunotherapy, such as metoprolol (metoprolol) and pembrolizumab (pembrolizumab), simultaneously?

Management of Beta-Blockers with Cancer Immunotherapy (Pembrolizumab)

Beta-blockers like metoprolol can be safely continued with cancer immunotherapy such as pembrolizumab, as the concerns about beta-blocker use apply specifically to allergen immunotherapy (for environmental allergies), not to immune checkpoint inhibitors used in cancer treatment. 1

Key Distinction: Allergen vs. Cancer Immunotherapy

The evidence provided addresses allergen immunotherapy (AIT) for inhalant allergies and venom hypersensitivity—not cancer immunotherapy with checkpoint inhibitors like pembrolizumab. These are fundamentally different treatments with distinct risk profiles:

• Allergen immunotherapy involves deliberate exposure to allergens that can trigger anaphylaxis, where beta-blockers interfere with epinephrine's ability to reverse anaphylactic reactions 2
• Cancer immunotherapy (pembrolizumab) works through PD-1 checkpoint inhibition and does not involve allergen exposure or significant anaphylaxis risk requiring epinephrine rescue 1

Evidence Supporting Concurrent Use

A phase I clinical trial specifically evaluated propranolol (a nonselective beta-blocker) combined with pembrolizumab in metastatic melanoma patients, demonstrating safety and promising efficacy. 1 Key findings:

• Nine patients received propranolol (10-30 mg twice daily) with pembrolizumab (200 mg every 3 weeks) 1
• No dose-limiting toxicities occurred 1
• Most common treatment-related adverse events were rash, fatigue, and vitiligo (44% of patients) 1
• Only one patient developed grade ≥3 adverse events 1
• Objective response rate was 78%, suggesting potential synergistic benefit 1

Clinical Management Approach

For Patients on Beta-Blockers Starting Pembrolizumab:

• Continue the beta-blocker (metoprolol or other agents) without interruption 1
• Monitor for standard immune-related adverse events from pembrolizumab (pneumonitis, colitis, hepatitis, endocrinopathies) 3
• Be aware that pembrolizumab can rarely cause cardiopulmonary toxicity including pulmonary hypertension, though this is unrelated to beta-blocker use 3

Monitoring Considerations:

• Assess cardiovascular status at baseline, particularly if the patient has underlying cardiac disease requiring beta-blocker therapy 2
• Continue beta-blockers in patients with heart failure and reduced ejection fraction using evidence-based agents (metoprolol succinate, carvedilol, or bisoprolol) 2
• Watch for immune-related cardiac adverse effects from pembrolizumab, which can occur independently of beta-blocker therapy 3

Important Caveats

Do not confuse this scenario with allergen immunotherapy guidelines. The extensive literature about beta-blocker risks with allergen immunotherapy 2 does not apply to cancer immunotherapy. Those guidelines address:

• Risk of severe anaphylaxis to allergen injections being refractory to epinephrine treatment due to unopposed alpha-adrenergic vasoconstriction 2
• Need for shared decision-making about discontinuing beta-blockers before starting allergen immunotherapy for inhalant allergies 2
• Special consideration for venom immunotherapy where life-threatening sting reactions may justify continuing beta-blockers 2, 4

None of these allergen immunotherapy concerns are relevant to pembrolizumab treatment.

Potential Synergistic Benefit

Emerging evidence suggests beta-blockers may actually enhance cancer immunotherapy efficacy by reducing stress-related immunosuppression in the tumor microenvironment, particularly through β2-adrenergic receptor blockade. 1 This represents a potential therapeutic advantage rather than a contraindication.