Re-challenge of immune checkpoint inhibitor pembrolizumab with concurrent tocilizumab after prior grade 3 pneumonitis.

ABSTRACT

Immune checkpoint inhibitors (ICIs) are associated with specific immune-related adverse events (irAEs) which are unique compared to cytotoxic chemotherapy. For life-threatening adverse events including grade 3 or more, permanent discontinuation of the ICIs is recommended, albeit without much robust evidence. Safe re-challenge of ICIs with concurrent immunosuppression has been reported with irAEs like gastrointestinal toxicity and arthritis. Here we present a case of a lady with undifferentiated pleomorphic sarcoma with programmed death ligand1 expression, who showed a complete response to pembrolizumab used as third-line therapy. However, it had to be stopped after 22 doses when the patient developed grade 3 pneumonitis. In view of progression off pembrolizumab, and lack of other effective alternatives, pembrolizumab was re-challenged with concurrent interleukin-6 (IL-6) blockade using tocilizumab. This was based on preliminary evidence on the role of IL-6 in mediating the irAEs, especially pneumonitis. The patient re-attained a complete response with pembrolizumab. There was no recurrence of the pneumonitis after rechallenging, and there was partial radiographic resolution of the ICI-interstitial lung disease after the combination therapy.