Cured or Not? Long-term Outcomes of Immunotherapy Responders. Focus on Melanoma

Immune checkpoint inhibitors (ICIs) demonstrated robust antitumor activity and tolerable safety in advanced melanoma. Data on long-term outcome of patients who benefited from this therapy and who are still free of progression despite ICI discontinuation is now available. We review here the characteristics of long-term ICI responders and address the critical question of cure.

Long-term outcome of patients with metastatic melanoma enrolled in large phase 2 and phase 3 clinical trials evaluating ICI in metastatic melanoma is now available. Durable responses, with more than 6 years of median follow-up, may persist after discontinuation. They occur more frequently in patients who achieved a complete response rather than in patients who had partial response or stable disease. Although long-term clinical benefit is more frequent in patients with high PDL-1 expression and smaller tumor burden, durable response may also be observed regardless of baseline characteristics. In patients with asymptomatic brain metastasis, combined immunotherapy (ipilimumab plus nivolumab) may also lead to long-term remission. Clinical trials confirm the durable antitumor activity of ICI. Although the hope for cure seems reasonable for many patients in this situation, late relapses may occur and no relapse-predictive biomarkers have been identified yet. Long-term responders who relapse can respond to a rechallenge of ICI although data are limited concerning the rate and the duration of this new response.