The approval of tumor-infiltrating lymphocyte (TIL) therapy in 2024 marked a pivotal advance in melanoma treatment, representing the first cellular therapy approved for a solid tumor.1 This autologous approach harnesses the patient’s own tumor-reactive lymphocytes, offering a treatment option for patients with unresectable or metastatic melanoma who have progressed on anti-PD-1 therapy and, when applicable, BRAF/MEK targeted therapies.2
Clinical trial data demonstrate that TIL therapy can produce durable responses in checkpoint inhibitor-refractory disease, with a substantial proportion of responders maintaining clinical benefit at 12 months.1 Early evidence suggests response rates may be higher in patients with lower tumor burden or less advanced disease stage, highlighting the importance of timing in treatment sequencing.1,3 The safety profile differs notably from CAR T-cell therapy used in hematologic malignancies. While toxicities including anemia, fevers, and thrombocytopenia occur primarily related to lymphodepletion and IL-2 administration, the concerning cytokine release syndrome and neurologic adverse events associated with CAR-T have not been observed with TIL therapy.1,2
Patient selection requires careful consideration of performance status, organ function, and disease characteristics.2 Multidisciplinary evaluation helps identify appropriate candidates who can tolerate the lymphodepletion regimen and IL-2 support required for successful TIL expansion and engraftment. The manufacturing timeline, typically requiring several weeks from tumor tissue procurement to TIL infusion, makes this approach less suitable for rapidly progressing disease.2 Patients with slowly progressing disease, particularly those with soft tissue tumors and shorter duration of prior anti-PD-1 exposure, may be better suited for this therapeutic approach.2
As cellular immunotherapy continues to evolve, clinicians should remain informed about eligibility criteria and referral pathways for these therapies. For patients facing limited options after standard immunotherapy failure, TIL therapy represents an important consideration in the treatment algorithm, and timely referral to centers offering these approaches may expand therapeutic opportunities.2,3
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