Management of checkpoint inhibitor toxicity and survival in patients with advanced melanoma

Autor: Olivier Jules van Not, Rik Jasper Verheijden, Alfonsus Johannes Maria van den Eertwegh, John B. A. G. Haanen, Christian U. Blank, Maureen J.B. Aarts, Franchette Van Den Berkmortel, Jan Willem de Groot, Geke Hospers, Ellen Kapiteijn, Melissa Melanie de Meza, Djura Piersma, Rozemarijn Van Rijn, Marion Stevense - den Boer, Astrid Aplonia Maria Van Der Veldt, Gerard Vreugdenhil, Marye J. Boers-Sonderen, Willeke Blokx, Michel W.J.M. Wouters, Karijn Suijkerbuijk
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:9546-9546
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2022.40.16_suppl.9546
Popis: 9546 Background: Management of checkpoint-inhibitor-induced immune-related adverse events (irAEs) is primarily based on expert opinion. Recent studies have suggested detrimental effects of immunosuppressive treatment with anti-TNF on checkpoint-inhibitor efficacy. Methods: Advanced melanoma patients experiencing grade ≥3 irAEs after treatment with first-line ipilimumab-nivolumab between 2015 and 2021 were included from the Dutch Melanoma Treatment Registry. Progression-free survival (PFS), overall survival (OS) and melanoma-specific survival (MSS) were analyzed according to toxicity management regimen. A cox proportional hazards model was used to account for the confounders age, sex, performance status, lactate dehydrogenase, site of metastases and type of irAE. Results: Out of 771 ipilimumab-nivolumab treated patients, 350 were treated with immunosuppression for severe irAEs. Of these patients, 235 received steroids only and 115 received steroids with second-line immunosuppressants consisting of anti-TNF, mycophenolic acid, tacrolimus and other immunosuppressants. Median PFS was significantly longer for patients treated with steroids (11.3 months) than for patients treated with steroids and second-line immunosuppressants (5.4 months; HR 1.43; 95%CI 1.07-1.90; p = 0.01). Median OS was also significantly longer for the steroids group (46.1 months) than for the steroids and second-line immunosuppressants group (22.5 months; HR 1.64; 95%CI 1.16-2.32; p = 0.005). Results for MSS were similar (not reached versus 28.8 months; HR 1.70; 95%CI 1.16-2.49; p = 0.006). Median PFS, OS and MSS are shown in Table 1. After adjustment for potential confounders, patients treated with steroids + second-line immunosuppressants showed a non-significant trend towards a higher risk of progression (HRadj 1.40; 95%CI 1.00-1.97; p = 0.05), a higher risk of death (HRadj 1.54; 95%CI 1.03-2.30; p = 0.04) and of melanoma-specific death (HRadj 1.62; 95%CI 1.04-2.51; p = 0.032) compared to the steroids group. Conclusions: Second-line immunosuppression for irAEs is associated with impaired PFS, OS, and MSS in advanced melanoma patients treated with first-line ipilimumab-nivolumab, irrespective of being anti-TNF or other second-line immunosuppressants. These findings stress the importance of assessing the effects of differential irAE management strategies, not only in melanoma but also in other tumor types. [Table: see text]
Databáze: OpenAIRE
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