Clinical Scorecard: Repeated administration of autologous tumor-infiltrating lymphocytes (LM103 infusion) alongside immune checkpoint inhibitors results in sustained tumor regression in a patient with advanced mucosal melanoma: a case study and review of existing literature

At a Glance

Key Highlights

• Multiple sequential autologous TIL infusions combined with anti-PD-1 therapy induced repeated clinical responses including partial and complete tumor regressions in a heavily pretreated patient.
• Longitudinal immune monitoring demonstrated sustained systemic immune activation correlating with clinical outcomes.
• TIL therapy shows potential for durable responses and long-term survival benefits even in immune checkpoint inhibitor-resistant melanoma.

Guideline-Based Recommendations

Diagnosis

• Confirm diagnosis of mucosal malignant melanoma by pathology and imaging.
• Assess prior treatment history including immune checkpoint inhibitor exposure.

Management

• Administer lymphodepletion chemotherapy with cyclophosphamide and fludarabine prior to TIL infusion.
• Infuse autologous TIL intravenously followed by high-dose interleukin-2 to support T-cell expansion.
• Consider repeated TIL infusions in patients with initial response and subsequent relapse.
• Combine TIL therapy with immune checkpoint inhibitors to enhance anti-tumor activity.

Monitoring & Follow-up

• Perform serial peripheral blood immune cell phenotyping and cytokine profiling to monitor systemic immune responses.
• Monitor tumor response by imaging at defined intervals post-infusion (e.g., 6 and 12 weeks).
• Observe and manage adverse events promptly, noting that they are generally manageable and transient.

Risks

• Potential for tumor relapse despite initial response to TIL therapy.
• Adverse events related to lymphodepletion, high-dose IL-2, and immune activation, which are generally manageable.

Patient & Prescribing Data

Heavily pretreated advanced melanoma patients refractory to multiple lines of immunotherapy including anti-PD-1 and CTLA-4 inhibitors.

Sequential TIL infusions can induce repeated clinical responses; combination with checkpoint inhibitors may improve efficacy; adverse events are manageable and transient.

Clinical Best Practices

• Ensure GMP-compliant manufacturing of autologous TIL products with quality control for sterility, viability, and potency.
• Use lymphodepletion chemotherapy to optimize TIL engraftment prior to infusion.
• Administer high-dose IL-2 post-TIL infusion to support T-cell expansion and persistence.
• Implement longitudinal immune monitoring to correlate immune activation with clinical outcomes.
• Consider multiple TIL infusions for patients with relapse after initial response.
• Combine TIL therapy with immune checkpoint inhibitors to enhance anti-tumor responses.

References

• Clinical trial registrations NCT06697665, NCT05941936, NCT05971589