What are the considerations for immunotherapy (ICI) in patients with a high 90-day mortality/hospice rate?

Considerations for Immunotherapy (ICI) in Patients with High 90-Day Mortality/Hospice Rate

Immunotherapy should be avoided in ICI-naive patients with poor performance status as they have a 77.1% mortality/hospice rate at 90 days with a median time to death of only 29 days.

Patient Selection Considerations

Key Prognostic Factors

• Prior ICI exposure is critical:

  • ICI-naive patients: 77.1% dead/hospice at 90 days; median time to death/hospice was 29 days
  • Previously treated patients: 38.6% dead/hospice at 90 days; median time to death/hospice was 242 days
  • Hazard ratio: 2.74 (95% CI: 1.2-6.25; p = 0.0121)

• Overall poor outcomes:

  • 90-day mortality/hospice rate: 68.2%
  • 90-day survival: Only 47.1% alive
  • Median overall survival: 81 days from first ICI dose
  • Median time to death/hospice: 35 days

Risk-Benefit Assessment Algorithm

1. Assess prior ICI exposure:

   • If previously treated with ICI → Consider continuing immunotherapy (better survival outcomes)
   • If ICI-naive → High risk of early mortality; consider alternatives

2. Evaluate hospital course metrics:

   • Median length of stay: 20 days from admission, 10 days from ICI start
   • Post-discharge continuation rate: Only 27.8% of discharged patients received additional immunotherapy

3. Consider fatal immune-related adverse events (irAEs):

   • Fatal irAE rates: anti-PD-1 (0.36%), anti-PD-L1 (0.38%), anti-CTLA-4 (1.08%), combination therapy (1.23%) 1
   • Myocarditis has highest fatality rate (39.7%) among irAEs 1
   • Fatal irAEs occur earlier with combination therapy (median 14.5 days) than monotherapy (median 40 days) 1

Special Populations Considerations

Elderly Patients

• Geriatric assessment (GA) is essential before initiating immunotherapy in older adults 1
• Older adults who screen positive for frailty using the G-8 (60%) experience higher hospitalization rates and shorter survival with immunotherapy 1
• Adults ≥90 years discontinue immunotherapy due to adverse events more than twice as often as younger patients 1

Patients with Autoimmune Disease

• ICI can be offered to patients with non-life-threatening and quiescent autoimmune diseases 1
• Higher incidence of irAEs in patients with autoimmune disease, though mostly mild 1
• Grade 3 or higher irAEs and discontinuation rates are 11% and 14%, respectively 1
• Close monitoring is highly recommended 1

Practical Management Approach

For ICI-naive patients with poor prognosis:

• Consider palliative care rather than immunotherapy initiation
• If proceeding with ICI, prepare for short duration of therapy (median 35 days to death/hospice)
• Discuss realistic expectations with patient/family (only 22.9% alive at 90 days)

For previously treated patients:

• More favorable risk-benefit profile (median 242 days to death/hospice)
• Higher likelihood of surviving beyond 90 days (61.4%)
• Monitor closely for irAEs, particularly in first 40 days of therapy

Pitfalls and Caveats

• Baseline corticosteroid use for palliative purposes is associated with worse outcomes (OS: 2.2 versus 11.2 months) 1
• Corticosteroids for non-cancer indications do not significantly impact survival 1
• Early discontinuation due to irAEs may not compromise survival benefit 1
• Pseudoprogression and hyperprogression can complicate assessment of treatment response 2

In conclusion, the decision to use immunotherapy in patients with high 90-day mortality risk should primarily be guided by prior ICI exposure status, with extreme caution in ICI-naive patients given their dismal prognosis and limited benefit.