Salvage Metastasectomy After Adoptive Cell Transfer for Melanoma: Long-Term Updates

Adoptive cell transfer (ACT) can mediate durable regression in patients with metastatic melanoma, and some patients with initial response may progress, requiring salvage therapy.

We report updated follow-up on a retrospective review of patients with metastatic melanoma receiving ACT at a single institution from 2000 to 2022. We identified patients with objective response (RECIST 1.0) or stable disease for at least 6 months (SD6) before experiencing oligoprogression in up to three extracranial sites managed with surgery. The primary outcomes were progression-free survival (PFS) and overall survival (OS) after surgery. We also performed an exploratory analysis for genomic mechanisms of tumor escape.

In total, 138 patients with metastatic melanoma treated with ACT had an objective response or SD6 before experiencing disease progression. Of these, 30 (21%) had extracranial oligoprogression managed with metastasectomy. With a median follow-up of 132 months (range 5-248), median OS was not reached and median PFS was 10.5 months. Ten-year OS was 54.7% and plateaued after 6 years. Four patients with pre- and post-ACT tumor sequencing demonstrated significant mutational evolution, with one patient experiencing loss of two major histocompatibility complex class I-restricted neoantigens recognized by T cells in the original infusion product.

Of patients experiencing oligoprogression after initial response to ACT (complete response, partial response, or SD6), 27% derived durable disease control after surgical management, confirming a potentially viable salvage option for "local" failures following ACT that may not portend systemic failure. Additional factors related to ACT response and oligoprogression that may guide patient selection for salvage metastasectomy remain undefined.