The advent of immune checkpoint inhibitors (ICI) has changed the landscape of oncological treatment for many forms of cancers including melanomas and lung cancers.1,2 However, these agents are associated with a unique array of immune-related adverse events (irAEs) with current guidelines stipulating permanent discontinuation of ICI if a grade 3-4 irAE occurred.3 Case reports are emerging that rechallenge with ICI following acute management of a grade 3-4 irAE is feasible and may be associated with durability of disease control.4 This study examined the toxicities and durability of disease response following rechallenge of ICI post grade 3-4 irAE.
A retrospective cross-sectional study was conducted amongst stage 3-4 melanoma or non-small cell lung cancer patients (aged≥18) treated with immunotherapy (pembrolizumab, ipilimumab, nivolumab or a combination) between 2014 and 2017. Severity of irAE were graded based on EVIQ guidelines and timing and nature of irAEs were obtained from electronic medical records.5
Amongst 176 patients eligible, 25 patients (14.2%) experienced a Grade 3-4 irAE and 16 patients (12 males, 4 females) were rechallenged with ICI. Amongst those who were rechallenged, initial irAE by nature: hepatitis (31.3%); colitis (37.5%); endocrine dysfunction: (12.5%); cutaneous: (18.8%). 81.3% received more than 1 cycle of ICI post-rechallenge (range: 1 to 35). Upon rechallenge, 25.0% experienced another Grade 3-4 irAE (50% experienced recurrence of initial toxicity; 50% experienced irAE of a different nature) with one resultant death from staphylococcus septicaemia secondary to refractory colitis. Post-rechallenge with ICI: 25.0% progressed on subsequent scan; 6.3% demonstrated regression; 25.0% remained stable with ongoing ICI; 31.3% stable on surveillance; and 12.5% died prior to repeat scans.
This study demonstrates that rechallenge with ICI post Grade 3-4 irAE may not be associated with recurrence of irAE. Durability of response post-rechallenge is demonstrated in 64.2% with stable disease on ICI or surveillance.