Multiple autologous tumor-infiltrating lymphocyte (LM103 infusion) therapy combined with immune checkpoint inhibitor induces repeated tumor regression in a patient with aggressive mucosal melanoma: a case report and literature review

Tumor-infiltrating lymphocyte (TIL) therapy was approved as a one-dose treatment indicated for melanoma patients who have progressed on anti-PD-1 therapy. However, the majority of patients show only short-duration responses, highlighting the urgent need to explore multiple cycles of TIL therapy and combination strategies. We report a case of a patient with aggressive stage IV nasal mucosal malignant melanoma with disease progression on multiple lines of immunotherapy who was enrolled in a clinical trial evaluating the safety and efficacy of autologous TIL therapy. Prior to TIL infusion, the patient underwent lymphodepletion with cyclophosphamide followed by fludarabine for 5 days. Approximately 24 hours later, the patient received an intravenous infusion of autologous TIL, followed by high-dose interleukin-2 for 6 days to support T-cell expansion and persistence. The patient achieved a partial response (PR) at 6 weeks and a complete response (CR) at 12 weeks post-infusion. However, tumor relapse occurred 7 months later. The patient then received a second TIL infusion, resulting in stable disease (SD) with transient shrinkage, but rapid regrowth occurred within 3 weeks. The patient subsequently received a third TIL infusion and achieved another PR within 2 weeks. Manageable adverse events were observed and resolved shortly after TIL treatments. A time-course study of peripheral blood cell subtyping and cytokine secretion demonstrated a long-term immune response. Longitudinal immune monitoring revealed sustained systemic immune activation. This case report shows that multiple autologous TIL therapies can induce repeated clinical and immunological responses in a heavily anti-PD-1-pretreated patient with advanced melanoma, underscoring the feasibility and therapeutic potential of multiple TIL treatments. Clinical trial registration: https://clinicaltrials.gov , identifier NCT06697665, NCT05941936, NCT05971589.