Immune-Related Tumor Response Dynamics As A Marker For Survival And Treatment Benefit During Pd-1 Inhibitor Therapy.

9521 Background: PD-1 inhibitors are promising anti-cancer agents and are associated with unique immune-related response patterns. We characterized patterns of tumor response dynamics on CT scans during PD-1 inhibitor therapy and investigated the association with overall survival (OS) in advanced melanoma patients (pts). Methods: Forty-nine advanced melanoma pts (22 males; median age: 55) treated with single-agent pembrolizumab at DFCI were retrospectively studied. Baseline and all follow-up CT during therapy were reviewed to quantify tumor burden using irRECIST, which uses unidimensional measurements and includes new lesions in tumor burden [Clin Cancer Res. 2013;19:3936-43]. Association between OS and tumor burden dynamics was studied. Results: Tumor burden change at best overall response ranged from -100% to 357% (median:-11%). Response rate was 41% (20/49; irCR in 4, irPR in 16). Spiderplot showed 3 distinct patterns of tumor response dynamics: A) tumor burden < 20% increase from baseline throughout therapy (n = 27, 55%); B) tumor burden ≥ 20% increase from baseline without subsequent response (n = 19, 39%); and C) pseudoprogression with initial tumor burden increase ( ≥ 20%) and subsequent response (n = 3, 6%). Pseudoprogressors were younger than others (median age: 40 vs. 56; p = 0.05), and achieved response after irPD was confirmed on 2 consecutive scans. Using a 3-month landmark analysis, pts with < 20% tumor burden increase from baseline at 3 months had longer OS than pts with ≥ 20% increase (12-month OS rate: 78 vs 51%). In extended Cox models, pts with < 20% tumor burden increase during therapy had significantly reduced hazards of death (HR = 0.16, 95% CI (0.05 - 0.54), p = 0.003 univariate; HR = 0.14, 95% CI (0.04 - 0.48), p = 0.002 multivariable). Conclusions: Three distinct patterns of tumor response dynamics were noted during pembrolizumab therapy. Pseudoprogressors achieved response after experiencing confirmed irPD, indicating a limitation of the current strategy for immune-related response evaluation. Tumor burden < 20% increase from baseline on follow-up CT scans was associated with longer OS, proposing a practical marker for survival and treatment benefit of PD-1 inhibitor therapy.