Rosemarie Mick

Supplementary Table S1. Baseline patient and disease characteristics.

Supplementary Table S2. Representativeness of Study Participants.

Supplementary Figure S3. CD8 T cells from patient 5 display an exhausted phenotype.

Purpose:Immunologic response to anti–programmed cell death protein 1 (PD-1) therapy can occur rapidly with T-cell responses detectable in as little as one week. Given that activated immune cells are FDG avid, we hypothesized that an early FDG PET/CT obtained approximately 1 week after starting pembrolizumab could be used to visualize a metabolic flare (MF), with increased tumor FDG activity due to infiltration by activated immune cells, or a metabolic response (MR), due to tumor cell death, that would predict response.Patients and Methods:Nineteen patients with advanced melanoma scheduled to receive pembrolizumab were prospectively enrolled. FDG PET/CT imaging was performed at baseline and approximately 1 week after starting treatment. FDG PET/CT scans were evaluated for changes in maximum standardized uptake value (SUVmax) and thresholds were identified by ROC analysis; MF was defined as >70% increase in tumor SUVmax, and MR as >30% decrease in tumor SUVmax.Results:An MF or MR was identified in 6 of 11 (55%) responders and 0 of 8 (0%) nonresponders, with an objective response rate (ORR) of 100% in the MF-MR group and an ORR of 38% in the stable metabolism (SM) group. An MF or MR was associated with T-cell reinvigoration in the peripheral blood and immune infiltration in the tumor. Overall survival at 3 years was 83% in the MF-MR group and 62% in the SM group. Median progression-free survival (PFS) was >38 months (median not reached) in the MF-MR group and 2.8 months (95% confidence interval, 0.3–5.2) in the SM group (P = 0.017).Conclusions:Early FDG PET/CT can identify metabolic changes in melanoma metastases that are potentially predictive of response to pembrolizumab and significantly correlated with PFS.

Supplementary Table S1. Baseline patient and disease characteristics.

Supplementary Figure S1. Analysis of Ki67+ CD8 T cells in peripheral blood.

Supplementary Figure S1. Analysis of Ki67+ CD8 T cells in peripheral blood.

Supplementary Figure S2. Change in SUVmax versus percentage of Ki67+ CD8 T cells.

Supplementary Figure S4. Early FDG PET/CT guides patient management.

Supplementary Table S3. PET imaging results and response assessments for all patients.