TY - JOUR T1 - Radiological dynamics and SITC-defined resistance types of advanced melanoma during anti-PD-1 monotherapy: an independent single-blind observational study on an international cohort JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-002092 VL - 9 IS - 2 SP - e002092 AU - Xue Bai AU - Michelle Kim AU - Gyulnara Kasumova AU - Lu Si AU - Bixia Tang AU - Chuanliang Cui AU - Xiaoling Yang AU - Xiaoting Wei AU - Justine Cohen AU - Donald Lawrence AU - Christine Freedman AU - Riley Fadden AU - Krista Rubin AU - Tatyana Sharova AU - Dennie Frederick AU - Keith Flaherty AU - Ryan Sullivan AU - Jun Guo AU - Genevieve Boland Y1 - 2021/02/01 UR - http://jitc.bmj.com/content/9/2/e002092.abstract N2 - Background Although the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Taskforce recently defined primary and secondary resistance to anti-programmed cell death protein 1 (anti-PD-1) therapy, there is lack of real-world data regarding differences in these resistance subtypes with respect to radiological dynamics and clinical manifestations.Methods We performed single-blind re-evaluations of radiological images by independent radiologists on a retrospectively assembled cohort of patients with advanced melanoma (n=254, median follow-up 31 months) receiving anti-PD-1 monotherapy at Massachusetts General Hospital and Peking University Cancer Hospital. Radiological characteristics and timing at multiple crucial time points were analyzed and correlated with each other and with survival. Primary and secondary resistance was defined as per the SITC Immunotherapy Resistance Taskforce definitions.Results The most significant target lesion measurement change took place within the first 3 months after anti-PD-1 initiation. Patients with stable disease with versus without tumor shrinkage at the initial evaluation exhibited distinct disease trajectory, as the rate of further upgrade to a partial or complete remission (CR/PR) was 44% and 0%, respectively. Eleven per cent of PR patients ultimately achieved a CR. In multivariate analyses, deeper response depth was independently associated with a more limited progression pattern, fewer involved organs, lower tumor burden, slower growth rate at disease progression (PD) (all p≤0.001), and longer post-progression survival (PPS) (bivariate analysis, p=0.005). Compared with primary resistance, secondary resistance was associated with less widespread PD pattern, lower tumor burden and slower tumor growth (all p≤0.001). Patients with secondary resistance were less likely to receive further systemic therapy (28% vs 57%, p<0.001) yet had significantly better PPS (HR 0.503, 95% CI 0.288 to 0.879, p=0.02).Conclusions Radiological dynamics were variable, yet significantly correlated with survival outcomes. SITC-defined primary and secondary resistance are distinct clinical manifestations in patients with melanoma, suggesting the possibility of resistance-type-based therapeutic decision-making and clinical trial design, once further validated by future prospective studies. ER -