Patterns of response to anti-PD-1 treatment: an exploratory comparison of four radiological response criteria and associations with overall survival in metastatic melanoma patients

Background: Radiological assessment of response to checkpoint inhibitors remains imperfect. We evaluated individual lesion and inter-patient response by response evaluation (RECIST) 1.1, immune-related response criteria (irRC), CHOI and modified CHOI (mCHOI) and correlated response with overall survival (OS). Methods: Thirty-seven patients with 567 measurable lesions treated with pembrolizumab in the Keynote 001 trial were studied. Association of response with OS was determined. Results: Response varied according to site; lung lesions had the highest rate of complete response (69 out of 163 (42%) vs other sites 71 out of 404 (18%), P<0.0001). Delayed response post first scan was seen in 2 out of 37 (5%) deemed progressive (PD) by RECIST and 2 out of 14 (14%) deemed PD by irRC. Modified CHOI criteria showed response of 38% (14 out of 37). Change in tumour size and density on first follow-up assessment was associated with OS with each 1000mm(2) increase in tumour size from baseline increasing the hazard of dying by 25.9% (HR = 1.259, (95% CI = 1.116-1.420), P = 0.0002). Similarly, each 20HU increase in density increased the HR by 15% (HR = 1.15, (95% CI 1.045-1.260), P = 0.004). Response defined by any criteria had superior OS (CHOI P = 0.0084; mCHOI P = 0.0183; irRC P<0.0001 and RECIST P = 0.0003). Conclusions: Response by any criterion was prognostic. Novel patterns of response and changes on treatment in tumour density suggest complex anti-tumour responses to immunotherapy.