Can empirical immune therapy be given to a patient with adenocarcinoma of the lung on High Flow Nasal Cannula (HFNC) with high Fraction of Inspired Oxygen (FiO2) and significant respiratory compromise, who also has uncontrolled diabetes and is taking antipsychotic medications?

Empirical Immunotherapy for Advanced Lung Adenocarcinoma in a Critically Ill Patient

Empirical immunotherapy is not recommended for a 75-year-old patient with lung adenocarcinoma on HFNC with FiO2 60%, flow 40L, uncontrolled diabetes, and on antipsychotic medications due to the high risk of adverse events and poor clinical outcomes in this critically ill state.

Patient Risk Assessment

• The patient is in acute hypoxemic respiratory failure requiring high levels of respiratory support (HFNC with FiO2 60%, flow 40L), indicating severe respiratory compromise 1, 2
• Advanced age (75 years) combined with multiple comorbidities (uncontrolled diabetes, respiratory failure) places the patient at higher risk for immune-related adverse events 1
• Antipsychotic medications may interact with immunotherapy and complicate management 1

Contraindications to Immunotherapy in This Setting

• History of potentially life-threatening conditions requiring immunosuppressive therapy is a major contraindication to immunotherapy, with 94% of experts considering this a reason not to give immunotherapy 1
• Poor performance status, which is likely in this critically ill patient on HFNC, is considered by 50% of experts as a contraindication to immunotherapy 1
• Advanced age combined with high disease burden (as evidenced by respiratory failure) is considered by 39% of experts as a reason to avoid immunotherapy 1

Respiratory Management Priorities

• The patient's immediate need is stabilization of respiratory status, as patients on HFNC with worsening hypoxemic respiratory failure require close monitoring for potential need for escalation to invasive mechanical ventilation 1
• HFNC therapy provides several benefits including:
  • Carbon dioxide washout from upper airways 3
  • Modest positive end-expiratory pressure effect 3, 2
  • Improved patient comfort compared to non-invasive ventilation 1, 2
• The patient should be monitored for signs of HFNC failure, which would necessitate escalation to invasive mechanical ventilation 1

Risks of Immunotherapy in Critical Illness

• Immunotherapy can cause immune-related adverse events (irAEs) that may worsen the patient's already critical condition 1
• Patients with severe COPD (which may be present given the respiratory failure) have shown significantly higher rates of irAEs (56%) compared to those with mild-moderate COPD (8.3-32.3%) or no COPD (21.1%) 4
• Uncontrolled diabetes represents a significant metabolic derangement that should be stabilized before considering immunotherapy 1
• Antipsychotic medications were an exclusion criterion in most immunotherapy clinical trials, and their interaction with immunotherapy is not well-studied 1

Appropriate Clinical Approach

• Prioritize respiratory stabilization and management of the acute hypoxemic respiratory failure 1
• Target oxygen saturation between 92-97% while on HFNC 1
• Monitor for signs of HFNC failure including increased respiratory rate, worsening hypoxemia, and altered mental status 1
• Address the uncontrolled diabetes as a priority before considering any cancer-directed therapy 1
• Once the patient is stabilized, comprehensive molecular testing should be performed to identify potential targetable mutations that might guide therapy selection 1

Future Considerations for Immunotherapy

• Once the patient is stabilized with improved respiratory status, controlled diabetes, and better performance status, immunotherapy could be reconsidered 1
• Molecular testing for PD-L1 expression and other biomarkers would help determine if the patient might benefit from immunotherapy in the future 1, 5
• The immune subtype of lung adenocarcinoma may influence response to immunotherapy, with "immune-hot" subtypes showing better response than "immune-cold" subtypes 6

In conclusion, while immunotherapy has revolutionized treatment for lung adenocarcinoma, the current critical clinical state of this patient with respiratory failure, uncontrolled diabetes, and antipsychotic medication use makes empirical immunotherapy too risky at this time. Stabilization of the patient's condition should be the priority before considering cancer-directed therapy.