TY - JOUR
T1 - A prediction model for response to immune checkpoint inhibition in advanced melanoma
AU - van Duin, Isabella A. J.
AU - Verheijden, Rik J.
AU - van Diest, Paul J.
AU - Blokx, Willeke A. M.
AU - El-Sharouni, Mary-Ann
AU - Verhoeff, Joost J. C.
AU - Leiner, Tim
AU - van den Eertwegh, Alfonsus J. M.
AU - de Groot, Jan Willem B.
AU - van Not, Olivier J.
AU - Aarts, Maureen J. B.
AU - van den Berkmortel, Franchette W. P. J.
AU - Blank, Christian U.
AU - Haanen, John B. A. G.
AU - Hospers, Geke A. P.
AU - Piersma, Djura
AU - van Rijn, Rozemarijn S.
AU - van Der Veldt, Astrid A. M.
AU - Vreugdenhil, Gerard
AU - Wouters, Michel W. J. M.
AU - Stevense-den Boer, Marion A. M.
AU - Boers-Sonderen, Marye J.
AU - Kapiteijn, Ellen
AU - Suijkerbuijk, Karijn P. M.
AU - Elias, Sjoerd G.
PY - 2024/5/15
Y1 - 2024/5/15
N2 - Predicting who will benefit from treatment with immune checkpoint inhibition (ICI) in patients with advanced melanoma is challenging. We developed a multivariable prediction model for response to ICI, using routinely available clinical data including primary melanoma characteristics. We used a population-based cohort of 3525 patients with advanced cutaneous melanoma treated with anti-PD-1-based therapy. Our prediction model for predicting response within 6 months after ICI initiation was internally validated with bootstrap resampling. Performance evaluation included calibration, discrimination and internal–external cross-validation. Included patients received anti-PD-1 monotherapy (n = 2366) or ipilimumab plus nivolumab (n = 1159) in any treatment line. The model included serum lactate dehydrogenase, World Health Organization performance score, type and line of ICI, disease stage and time to first distant recurrence—all at start of ICI—, and location and type of primary melanoma, the presence of satellites and/or in-transit metastases at primary diagnosis and sex. The over-optimism adjusted area under the receiver operating characteristic was 0.66 (95% CI: 0.64–0.66). The range of predicted response probabilities was 7%–81%. Based on these probabilities, patients were categorized into quartiles. Compared to the lowest response quartile, patients in the highest quartile had a significantly longer median progression-free survival (20.0 vs 2.8 months; P <.001) and median overall survival (62.0 vs 8.0 months; P <.001). Our prediction model, based on routinely available clinical variables and primary melanoma characteristics, predicts response to ICI in patients with advanced melanoma and discriminates well between treated patients with a very good and very poor prognosis.
AB - Predicting who will benefit from treatment with immune checkpoint inhibition (ICI) in patients with advanced melanoma is challenging. We developed a multivariable prediction model for response to ICI, using routinely available clinical data including primary melanoma characteristics. We used a population-based cohort of 3525 patients with advanced cutaneous melanoma treated with anti-PD-1-based therapy. Our prediction model for predicting response within 6 months after ICI initiation was internally validated with bootstrap resampling. Performance evaluation included calibration, discrimination and internal–external cross-validation. Included patients received anti-PD-1 monotherapy (n = 2366) or ipilimumab plus nivolumab (n = 1159) in any treatment line. The model included serum lactate dehydrogenase, World Health Organization performance score, type and line of ICI, disease stage and time to first distant recurrence—all at start of ICI—, and location and type of primary melanoma, the presence of satellites and/or in-transit metastases at primary diagnosis and sex. The over-optimism adjusted area under the receiver operating characteristic was 0.66 (95% CI: 0.64–0.66). The range of predicted response probabilities was 7%–81%. Based on these probabilities, patients were categorized into quartiles. Compared to the lowest response quartile, patients in the highest quartile had a significantly longer median progression-free survival (20.0 vs 2.8 months; P <.001) and median overall survival (62.0 vs 8.0 months; P <.001). Our prediction model, based on routinely available clinical variables and primary melanoma characteristics, predicts response to ICI in patients with advanced melanoma and discriminates well between treated patients with a very good and very poor prognosis.
KW - immune checkpoint inhibition
KW - immunotherapy
KW - melanoma
KW - prediction model
KW - response prediction
U2 - 10.1002/ijc.34853
DO - 10.1002/ijc.34853
M3 - Article
SN - 0020-7136
VL - 154
SP - 1760
EP - 1771
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 10
ER -