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Updated: Jun 19, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: a retrospective observational
Mehul Gupta1,2, Igor Stukalin1,2, Daniel E Meyers1,2
1Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Background:
The association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice.
Methods:
We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.1 assessed objective imaging response between patients receiving anti-programmed cell death protein 1 (anti-PD1) monotherapy and those receiving combination ipilimumab-nivolumab. Secondary outcomes were identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT).
Results:
198 patients were included, 41/198 (20.7%) had complete response, 86/198 (43.4%) had partial response, 23/198 (11.6%) had stable disease, and 48/198 (24.2%) had progressive disease. Median OS was not reached (NR) (95% CI 49.0-NR) months for complete responders, NR (95%CI 52.9-NR) months for partial responders, 33.7 (95%CI 15.8-NR) months for stable disease, and 6.4 (95%CI 5.2-10.1) months for progressive disease (log-rank p<0.001). Likelihood of objective imaging response remained similar between anti-PD1 monotherapy and ipilimumab-nivolumab groups (OR 1.95 95%CI 0.85-4.63, p=0.121). Elevated LDH level (OR 0.46; 95%CI 0.21-0.98, p=0.043), mucosal primary site (OR 0.14; 95%CI 0.03-0.48, p=0.003), and BRAF V600E mutation status (OR 0.31; 95%CI 0.13-0.72, p=0.007) were associated with decreased likelihood of response.
Conclusion:
No significant difference in likelihood of imaging response between anti-PD1 monotherapy and combination ipilimumab-nivolumab was observed. Elevated LDH level, mucosal primary site, and BRAF V600E mutation status were associated with decreased likelihood of response. Given that pivotal clinical trials of ipilimumab-nivolumab did not formally compare ipilimumab-nivolumab with nivolumab monotherapy, this work adds context to differences in outcomes when these agents are used. These results may inform treatment selection, and aid in counseling of patients treated with first-line ICI therapy in routine clinical practice settings.
Insights
First-line immune checkpoint inhibitor (ICI) therapy for advanced melanoma showed similar imaging response rates between anti-PD1 monotherapy and combination ipilimumab-nivolumab. Baseline factors like LDH, primary site, and BRAF mutation influence response likelihood.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Objective imaging response to first-line immune checkpoint inhibitors (ICIs) in advanced melanoma is not well-characterized in clinical practice.
- Understanding treatment efficacy in real-world settings is crucial for optimizing patient outcomes.
Purpose of the Study:
- To compare the likelihood of objective imaging response between anti-programmed cell death protein 1 (anti-PD1) monotherapy and combination ipilimumab-nivolumab in advanced melanoma patients.
- To identify baseline characteristics associated with non-response to first-line ICI therapy.
- To explore the association between imaging response and overall survival (OS) and time to next treatment (TTNT).
Main Methods:
- Multi-center retrospective cohort analysis of advanced melanoma patients receiving first-line ICI therapy (August 2013-May 2020).
- Primary outcome: RECIST v1.1 assessed objective imaging response.
- Secondary outcomes: Baseline factors associated with non-response, and association of imaging response with OS and TTNT.
Main Results:
- 198 patients included; objective response rates varied by disease status (complete, partial, stable, progressive).
- No significant difference in objective imaging response likelihood between anti-PD1 monotherapy and ipilimumab-nivolumab (OR 1.95, p=0.121).
- Elevated LDH, mucosal primary site, and BRAF V600E mutation were associated with decreased response likelihood (p<0.05).
Conclusions:
- First-line anti-PD1 monotherapy and ipilimumab-nivolumab demonstrate similar imaging response rates in advanced melanoma.
- Elevated LDH, mucosal primary site, and BRAF V600E mutation are predictive of poorer response.
- These findings provide valuable context for treatment selection and patient counseling in routine clinical practice.
