Real-world experience of immune checkpoint inhibitor (ICPI) mediated pneumonitis in patients with metastatic cancer treated at Cambridge University Hospitals NHS Foundation Trust (CUHFT)


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Orthi Shahzad1,James Jones2,Sarah Welsh2,Jurgen Herre2,Pippa Corrie2
1University of Cambridge,2Cambridge University Hospitals NHS Foundation Trust

Abstract

Background

Immune checkpoint inhibitors have had a significant impact in improving outcomes for patients with metastatic cancer. However, they are associated with novel immune-related adverse events (IrAE). One of these is pneumonitis, which is life-threatening and limits re-challenge with further immunotherapy. ‘Real-world’ off-trial data concerning the incidence, management and prognosis of ICPI-mediated pneumonitis is lacking.

Method

A retrospective analysis was conducted of patients who received ICPI at CUHFT ‘off-trial’ from 1stJanuary 2014 to 1stApril 2019 by review of electronic patient records. Those who developed pneumonitis were analysed in more detail to assess severity (CTCAE v5.0 criteria), associated clinical data, management and recovery trajectory.

Results

Pneumonitis occurred in 17 out of 308 patients (5.52%) on single agent and 4 out of 35 (11.43%) on dual agent (ipilimumab & nivolumab)treatment. The median number of days from first dose of ICPI to development of pneumonitis was 46 for single agent (range: 10-310) and 54.5 for dual agent (range: 39-200). 8 of the 21 (38.1%) affected patients had a previous history of respiratory disease whereas only 33 of 305 (10.8%) unaffected patients did.

 

18 of the 21 patients recovered from pneumonitis, the median time to clinical resolution was 18 days (range 2-69). 9 patients were hospitalised. 2 of the 3 patients who did not recover died due to pneumonitis (both on pembrolizumab), the 3rddied due to disease progression. All were treated with high dose steroids; the median duration of steroid treatment was 40 days (range 6-134). 5 patients restarted immunotherapy after recovery.

Conclusion

This real-world analysis supports published data on pneumonitis as a rare but potentially fatal complication of ICPI treatment. It highlights the importance of recognising pneumonitis quickly for the best care of patients on immunotherapy and the need for research into risk factors and optimal management strategies.