Immune checkpoint inhibitors (ICIs) have become standard of care in the management of advanced melanoma. While some evidence suggests that rechallenge in the setting of toxicity with prior ICIs is safe, there is rather limited evidence on the efficacy and safety of rechallenge with alternative ICI in the context of disease progression on initial ICI.
We retrospectively analysed all patients with advanced melanoma who received ICIs between March 2016 and August 2017 at our centre. We used i) RECIST criteria to estimate objective overall response rate (ORR) & ii) Kaplan-Meier method to calculate the progression-free survival (PFS) and overall survival (OS).
Overall, 60 melanoma patients received ICIs, 31 patients discontinued initial ICI due to toxicity (N = 7) or disease progression (N = 24). 17 patients (54.8%) were rechallenged with an alternative ICI and three (17.6%) were rechallenged again with a third ICI. Of the 17 rechallenged patients, their initial treatment was discontinued due to either disease progression (14/17, 82%) or toxicity (3/17, 18%). The types of ICIs in rechallenged patients were as follows: first ICI; ipilimumab [anti-CTLA4] (9), combination ipilimumab and nivolumab [anti-PD-1] (1) and pembrolizumab [anti-PD-1] (7) and subsequent ICI; pembrolizumab (10), ipilimumab (6) and nivolumab (1). The three patients rechallenged for a second time all received nivolumab. The ORR in rechallenged patients was 23.5% vs 51.2% in the non-rechallanged patients. Rates of adverse events were not significantly different compared to first ICIs (Grade 3 irAE: 17.5% vs 23.5%). The median PFS and OS of rechallenged patients were 20 months [95% CI: 3.9-36.0] and 29.4 months [95% CI: 14.6-44.3] respectively, compared to 4 months [95% CI: 1.1-6.8] and 8.4 months [95% CI: 1.9-14.8] for patients who discontinued but not rechallenged. The authors note that comparing these groups should be interpreted with caution as they may constitute different patient cohorts.
In the setting of disease progression or toxicity in the management of advanced melanoma with an initial ICI, rechallenge with alternative ICIs shows some ORR and reasonable PFS and OS. This strategy maybe a viable plan for selected patients.
Guy Faust.
Has not received any funding.
G. Faust: Educational sponsorship to conferences, advisory board: MSD, BMS. All other authors have declared no conflicts of interest.