Managing Pneumonitis Associated With PD1 Checkpoint Inhibitors in RCC
PD1 checkpoint inhibitors have become a key class of drugs in the arsenal for advanced renal cell carcinoma (RCC). It is critical that providers who prescribe immune checkpoint inhibitors have an understanding of the toxicity profile and how to manage potentially serious side effects. It is also critical to assure good patient education prior to administering them. Pneumonitis is a well-known, potentially serious toxicity, which is relatively uncommon. A study published in the December issue of JAMA Oncology evaluated pneumonitis associated with the use of PD1 inhibitors in several cancers.1
The study was a meta-analysis pooling data from 26 studies, 3 of which were RCC trials, and 4496 unique patients. The overall incidence of pneumonitis was 2.7% (95% CI, 1.9%–3.6%) for all grades and 0.8% (95% CI, 0.4–1.2%) for grade 3 or greater. Toxicity was generally greater with combination immunotherapy.
Presenting symptoms of pneumonitis can include new or worsening cough, chest pain, and shortness of breath. Some patients may be asymptomatic and have radiographic changes only. As providers, it is important to be familiar with the presentation and management strategies as outlined below.
Grade 1: Radiographic changes only
- Consider holding therapy.
- Closely monitor for worsening symptoms.
- Consider pulmonary and/or infectious disease consultation.
- Re-assess at 2- to 3-week intervals.
- If improved and treatment was held, resume when stable.
- If worsens, treat as grade 3/4 toxicity.
Grade 2: Mild to moderate symptoms or worsening from baseline
- Hold therapy.
- Monitor daily.
- Consult pulmonology and infectious disease.
- Consider bronchoscopy and/or lung biopsy.
- Start corticosteroids at a dose of 1 to 2 mg/kg/day prednisone or equivalent.
- Taper steroids over >4 weeks once improved to baseline.
- If no improvement or worsening in 2 weeks, treat as grade ¾.
Grade 3/4: Severe symptoms, new/worsening hypoxia, or life-threating symptoms ± hospitalization
- Permanently discontinue therapy.
- Monitor daily.
- Consult pulmonology and infectious disease.
- Consider bronchoscopy and/or lung biopsy.
- Start corticosteroids, 1 to 2 mg/kg/day prednisone (or equivalent).
- If improved to baseline, begin steroid taper over >4 weeks.
- If persists or worsens after 2 days, add non-corticosteroid immunosuppressant.
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