Immunotherapy Rechallenge Is Effective for Most Patients With Late Progression After Initial Ipilimumab + Nivolumab Response

Clinical benefit achieved with ipilimumab + nivolumab combination therapy is typically long lasting. However, late progression, after therapy completion, does occur in a subset of patients. At the time of late progression, immunotherapy options include anti-PD-1 monotherapy, anti-PD-1/LAG-3, repeat anti-PD-1/CTLA-4 therapy, or TIL therapy, but the efficacy of these approaches is unknown. To investigate, we evaluated 230 patients with advanced melanoma who received treatment with ipilimumab + nivolumab at Dana-Farber Cancer Institute between 2015 and 2022 as first-line treatment. Of these, 111 had an initial response of stable disease (SD) or better for 6 months or longer. Of the 111 deriving clinical benefit, 19 had late progression, 14 while off therapy. Ten of the 14 patients who had late progression off therapy were rechallenged with immune checkpoint inhibition (ICB), either as monotherapy or in combination. Eight out of those 10 patients had clinical benefit of SD or better upon ICB rechallenge. The two who did not benefit from rechallenge had mucosal melanoma (3 patients had mucosal, 7 had cutaneous). The data indicate that clinical benefit upon rechallenge with ICB can be achieved in the majority of patients, specifically those with the cutaneous subtype, although responses are mostly SD and are relatively short lived.