Complete metabolic response as early predictor of long-term efficacy after adoptive T cell therapy using tumor-infiltrating lymphocytes

<b>Introduction:</b> Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has proved to be an effective treatment for metastatic melanoma, even in patients failing anti-PD-1 blockade. Nevertheless, progression is observed in a substantial subgroup of patients following an initial objective response to treatment with TILs. These patients might benefit from additional consolidating treatment before clinical progression, but thus far, it is not possible to identify this subgroup of patients prone to progress. In this study the predictive value of early metabolic response after TIL therapy is explored.<b>Materials and methods:</b> 60 patients treated with TIL therapy in 4 different clinical trials and with available [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography-CT (FDG-PET/CT) scans at baseline and at least one follow-up scan 6-8 weeks and/or 12-16 weeks post-TIL infusion were included.<b>Results:</b> Obtaining complete metabolic response (CMR) was associated with significantly superior median overall survival (mOS) compared with not obtaining CMR (p<0.0001). Of particular interest, metabolic response divided RECIST partial responders (22 patients) into two groups with significantly different clinical outcomes. Neither mOS (range 32.2-149.8+) nor median progression-free survival (mPFS; range 20.7-123.4+) were reached for patients with partial response (PR)/CMR (10 patients), whereas patients with PR/non-CMR (12 patients) had a mOS of 28.7 months (p=0.0016) and a mPFS of 7.8 months (p<0.0001).Overall, not achieving a CMR was associated with a short mPFS of 3.2 months, and 97.9% (47/48) of all patients in this group progressed within 12 months.<b>Conclusion:</b> In conclusion, early CMR is a strong predictor of long-term survival after TIL therapy in metastatic melanoma patients. Furthermore, FDG-PET/CT scans appear superior to CT scans for providing early prognostic information after TIL therapy in melanoma and can be used to tailor patient-specific management and follow-up strategies.