From the Guidelines
For steroid-resistant immune checkpoint inhibitor (ICI) pneumonitis, I recommend escalating to additional immunosuppressive therapy, such as infliximab (5 mg/kg as a single dose, may repeat after 2 weeks if needed) or mycophenolate mofetil (1 g twice daily), as suggested by the most recent guidelines 1.
Key Considerations
- Permanently discontinue the ICI therapy to prevent further immune-mediated damage.
- Provide supportive care, including supplemental oxygen as needed, and consider empiric antibiotics to cover potential concurrent infections while awaiting culture results.
- Pulmonary and infectious disease consultation is strongly advised to guide management and monitor response.
- Serial chest imaging and pulmonary function tests should be used to assess the response to treatment.
Rationale
The rationale for additional immunosuppressants is to target different immune pathways when steroids alone are insufficient. ICI pneumonitis results from T-cell mediated inflammation in lung tissue, and agents like mycophenolate inhibit T-cell proliferation while infliximab blocks TNF-alpha, a key inflammatory cytokine. Early intervention with these second-line agents is crucial as steroid-resistant pneumonitis carries significant mortality risk, with some studies reporting rates of 30-40% in grade 3-4 cases 1.
Management Approach
- If there is no improvement within 72 hours of corticosteroid use, consultation with or referral to an expert should be arranged, and therapeutic escalation should occur, considering options like tocilizumab, infliximab, or IVIG 1.
- The choice of additional immunosuppressive therapy should be individualized based on the patient's clinical presentation, comorbidities, and potential side effects of the medications.
Monitoring and Follow-Up
- Close monitoring of the patient's symptoms, oxygen saturation, and pulmonary function is essential to assess the response to treatment and adjust the management plan as needed.
- Regular follow-up with pulmonary and infectious disease specialists is recommended to ensure optimal management of steroid-resistant ICI pneumonitis.
From the Research
Definition and Incidence of Steroid Resistant ICI Pneumonitis
- Steroid-refractory ICI-pneumonitis is defined as immune-checkpoint inhibitor (ICI)-pneumonitis that does not improve or resolve with corticosteroids and requires additional immunosuppression 2.
- The incidence of steroid-refractory ICI-pneumonitis is reported to be around 18.5% of patients with ICI-pneumonitis 2 and 10% of patients with pneumonitis treated with corticosteroids 3.
Clinical Features and Treatment
- Steroid-refractory ICI-pneumonitis often occurs early in patients' treatment courses and commonly exhibits a diffuse alveolar damage (DAD) radiographic pattern 2, 4.
- Treatment options for steroid-refractory ICI-pneumonitis include intravenous immunoglobulin (IVIG), infliximab, cyclophosphamide, and tacrolimus 2, 3, 4, 5.
- Pulse corticosteroid therapy has also been reported as a potential treatment option for steroid-refractory pneumonitis 5.
Outcomes and Mortality
- The mortality rate for patients with steroid-refractory ICI-pneumonitis is high, ranging from 67% to 100% in some studies 2, 3.
- Patients treated with IVIG alone may have improved survival compared to those treated with other immunosuppressants 2, 6.
- The use of cyclophosphamide as a treatment option for pneumonitis after corticosteroid failure may also be associated with improved outcomes 3, 4.
Risk Factors
- Pre-treatment pulmonary function tests (PFTs) and chest imaging abnormalities may be predictors of severe ICI-pneumonitis 6.
- Lower forced vital capacity percent predicted and lower total lung capacity percent predicted may be associated with severe disease 6.
- Initial corticosteroid dose of less than 1 milligram per kilogram prednisone equivalent may be correlated with partially steroid-responsive or steroid-refractory ICI-pneumonitis 6.