Related Experiment Video
Updated: Nov 16, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Radiological dynamics and SITC-defined resistance types of advanced melanoma during anti-PD-1 monotherapy: an
Xue Bai1,2, Michelle Kim3, Gyulnara Kasumova3
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China.
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.
Insights
Real-world data shows distinct radiological and clinical differences between primary and secondary resistance to anti-programmed cell death protein 1 (anti-PD-1) therapy in melanoma patients. Understanding these patterns can inform treatment decisions and clinical trial design.
Area of Science:
- Oncology
- Immunotherapy
- Radiology
Background:
- The Society for Immunotherapy of Cancer (SITC) defined primary and secondary resistance to anti-programmed cell death protein 1 (anti-PD-1) therapy.
- Real-world data is lacking on the radiological dynamics and clinical manifestations of these resistance subtypes.
Purpose of the Study:
- To analyze radiological dynamics and clinical manifestations of primary and secondary resistance to anti-PD-1 therapy in advanced melanoma patients.
- To correlate these resistance patterns with survival outcomes.
Main Methods:
- Retrospective analysis of 254 advanced melanoma patients treated with anti-PD-1 monotherapy.
- Single-blind re-evaluation of radiological images by independent radiologists.
- Correlation of radiological characteristics and timing with survival.
Main Results:
- Significant target lesion measurement changes occurred within the first 3 months of anti-PD-1 therapy.
- Deeper response depth correlated with limited progression, fewer organs involved, lower tumor burden, slower growth rate, and longer post-progression survival.
- Secondary resistance showed less widespread progression, lower tumor burden, and slower tumor growth compared to primary resistance, leading to better post-progression survival.
Conclusions:
- Radiological dynamics in anti-PD-1 therapy correlate significantly with survival outcomes in melanoma.
- SITC-defined primary and secondary resistance represent distinct clinical manifestations.
- These findings suggest potential for resistance-type-based therapeutic decision-making and clinical trial design.
