Severe pneumonitis refractory to steroids following anti-PD-1 immunotherapy

Abstract

Anti-programmed death 1 (PD-1) immune checkpoint inhibitors enhance the antitumour activity of the immune system and have produced durable tumour responses in several solid tumours including non-small cell lung cancer (NSCLC). However, PD-1 inhibitors can lead to immune-related adverse events , including pneumonitis, which is typically mild, but can be severe and potentially fatal. Pneumonitis often resolves with steroids, but some cases are steroid refractory, leading to a relapsing and remitting course in milder cases or the need for salvage therapies in more severe cases. Here, we present two patients with NSCLC who developed severe pneumonitis following therapy with nivolumab and pembrolizumab. While one patient improved with steroids and infliximab, the other patient failed to respond to steroids and subsequently died. These cases demonstrate the highly variable presentation and therapeutic responses seen in patients with pneumonitis following anti-PD-1 therapy and illustrate that severe cases can often present refractory to steroid therapy.

Steroid-refractory PD-(L)1 pneumonitis: incidence, clinical features, treatment, and outcomes

“…All patients in our series receiving infliximab were given one dose (5 mg/kg), which is in accordance with current published literature describing successful use of infliximab for steroid-refractory ICI-pneumonitis in selected cases. 10 13 After receiving infliximab, steroid-refractory ICI-pneumonitis worsened in one patient (grade 3 to grade 4) and improved in the other (grade 4 to grade 3).…”

“…6–9 However, the clinical and radiographic features of steroid-refractory ICI-pneumonitis are poorly understood and limited to individual cases and small case series. 10–13 Additionally, patients who develop steroid-refractory ICI-pneumonitis almost universally succumb to this toxicity or the infectious complications of immunosuppressive management. 2 14 …”

Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune‐related adverse events after immune checkpoint inhibitor therapy

“…Even with our improved management borne from greater experience, it is acknowledged that much of the current management of irAEs is extrapolated from other forms of autoimmune dysfunction. For example, variable efficacy of TNF inhibition to treat pneumonitis has been described in the limited available literature; steroid‐refractory pneumonitis does not to date appear to respond as reliably to immunosuppression as some other irAEs, such as colitis. Neither of the two patients in our series treated for pneumonitis responded to immunosuppression beyond corticosteroids.…”

The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients

“…Infliximab, a monoclonal anti-tumor necrosis factor-α (TNF-α) antibody, is recommended as the first-line immunosuppressive drug for steroid-refractory CIP. Although NSCLC patients with steroid-refractory CIP have benefited from infliximab 86 , the recommendation is based on extrapolation from the efficacy of infliximab in managing immune-related colitis and lacks pathophysiological support. Notably, infliximab itself can cause interstitial pneumonitis and liver injury 87 – 89 .…”