Repeated Autologous TIL Therapy with Checkpoint Inhibitors in Advanced Mucosal Melanoma

Overview

This case study reports sustained tumor regression in a patient with advanced nasal mucosal melanoma treated with three sequential autologous tumor-infiltrating lymphocyte (TIL) infusions combined with immune checkpoint inhibitors. The patient achieved partial and complete responses after initial and repeated TIL treatments, with manageable adverse events and evidence of long-term systemic immune activation.

Background

Tumor-infiltrating lymphocyte (TIL) therapy is an adoptive cell transfer approach approved for melanoma patients refractory to anti-PD-1 therapy, demonstrating durable responses in a subset of patients. Despite promising five-year survival data, most patients experience short-duration responses, prompting investigation into multiple TIL cycles and combination with immune checkpoint inhibitors. Mucosal melanoma is an aggressive subtype with limited treatment options, and repeated TIL infusions may offer a novel therapeutic strategy.

Data Highlights

Key Findings

• Multiple sequential autologous TIL infusions combined with anti-PD-1 therapy induced repeated clinical responses in a heavily pretreated advanced mucosal melanoma patient.
• The patient achieved a complete response after the first infusion and partial responses after subsequent infusions, demonstrating potential for repeated TIL therapy.
• Peripheral blood immune monitoring showed sustained systemic immune activation correlating with clinical responses.
• Adverse events related to TIL therapy were manageable and transient.
• This case supports the feasibility and therapeutic potential of multiple TIL treatments in ICI-refractory melanoma.

Clinical Implications

Repeated administration of autologous TIL therapy alongside immune checkpoint inhibitors may provide a viable treatment option for patients with advanced melanoma who have progressed on prior immunotherapies. Monitoring immune responses longitudinally can help correlate clinical outcomes with systemic immune activation, guiding personalized treatment strategies. Further clinical trials are warranted to optimize dosing schedules and patient selection for multiple TIL infusions.

Conclusion

This case demonstrates that multiple cycles of autologous TIL therapy combined with checkpoint blockade can induce sustained tumor regression and immune activation in advanced mucosal melanoma, highlighting the promise of repeated TIL treatments in refractory settings.

References

1. Lifileucel Phase II Trial 5-Year Follow-up -- Durable Clinical Outcomes in Advanced Melanoma
2. FDA Approval of TIL Therapy -- Emerging Adoptive Cellular Therapy for Solid Tumors
3. Combination Approaches of TIL and PD-1 Inhibitors -- Enhanced Anti-tumor Activity