Optimizing immune-related tumor response assessment: does reducing the number of lesions impact response assessment in melanoma patients treated with ipilimumab?

Background: Investigate the impact of the reduction of the number of target lesions on immune-related response assessment in advanced melanoma patients treated with ipilimumab. Method: Ninety patients (53 males, 37 females; age range: 25-87) with advanced melanoma treated with ipilimumab in two clinical trials were studied. Tumor measurements during trial allowing up to 5 lesions per organ and 10 lesions in total were retrospectively reviewed. A second set of tumor measurements allowing up to 2 lesions per organ and 5 lesions in total was generated. Immune-related response assessments by two measurements were compared. Results: The number of target lesions was significantly reduced when up to 2 per organ and 5 in total lesions were allowed (Wilcoxon P < 0.0001). The immune-related response assessment using reduced number of lesions was highly concordant with assessment using the original number of lesions (Spearman r for the percent change on 1st-3rd follow-up: 0.860-0.970; K-w for best immune-related response: 0.908). Median time-to-progression was 26.9 months (95% CI: 9.1-infinity) by both assessments. Interobserver agreement of measurements was high for both assessments, with the concordance correlation coefficient above 0.98. Conclusion: Reduction of the number of target lesions did not significantly affect immune-related response assessment or the measurement variability in advanced melanoma patients treated with ipilimumab. Using up to 2 per organ and 5 in total target lesions is proposed to assess immune-related response, while it is important to keep other novel features of immune-related response criteria such as confirmation of progression and inclusion of new lesion measurements.