Background: Anti-PD-1 therapy has demonstrated activity in MM however current data may not fully reflect patterns of response and relapse as discerned by comprehensive lesion-specific analysis. Methods: Bidimensional measurements of every metastasis ≥5mm (≥15mm short axis for lymph nodes [LN]) in MM patients enrolled in the MK3475–001 trial at a single centre were obtained on CT scans at baseline, 12 weeks and thereafter. Response of individual metastases was determined by change in product of longest perpendicular diameters (POD) and classified as complete (CR, disappearance or <10mm short axis for LN), partial (PR, ≥50% reduction in POD), stable (SD, neither CR/PR/PD) or progressive (PD, ≥25% increase in POD and ≥5mm in 1 axis). Overall patient response was determined using immune related response criteria (irRC). Results: Twenty-seven patients with median follow-up 54 weeks had a total of 442 discrete metastases at baseline (median 10/patient; range 2–68/patient; median POD 129mm2). 13/27 (48%) patients had an irRC objective response (OR), 11 (85%) by first scan. Although only 1/27 patients achieved CR (3.7%), 228/442 (52%) individual metastases underwent CR and 81% of patients (22/27) had ≥1 CR metastasis at first scan. CR metastases were smaller than non-CR [median POD 80 versus 246mm2(p < 0.05)] however 92/244 metastases (38%) ≥100mm2 reached CR. CR rate was highest in lung versus other sites combined (p < 0.05). Of 12 (44%) patients who progressed, only 1 had a prior OR. Ten patients (83%) progressed in new and existing metastases simultaneously; no site of progression predominated. Of 80 new or growing metastases at first scan, only 4 (5%) subsequently had OR. Conclusions: Response to anti-PD-1 therapy is rare in metastases that are new or growing at first scan. CR in individual metastases is common, sustained, and influenced by site and size. These results have implications for the biology of PD-1 inhibition, resistance and biomarker development.