1157P - Corticosteroids and second-line immunosuppressants for immune-related adverse events and melanoma survival

Background

Recent studies indicate an association between immunosuppressive medication for immune-related adverse events (irAEs) and impaired survival. Whether this is related to corticosteroids or second-line immunosuppressants (IS) is unknown. We assessed the association of immunosuppressive regimens with survival in patients with melanoma.

Methods

Patients with advanced melanoma who received IS for irAEs induced by first-line anti-PD-1+/-anti-CTLA-4 were included from 11 Dutch and Belgian hospitals. Associations of cumulative and peak doses of corticosteroids and use of second-line IS with progression free survival (PFS) from start of IS and overall survival (OS) since immune checkpoint inhibitor (ICI) initiation were assessed using multivariable Cox regression. Analyses were adjusted for sex, age, stage, performance status, LDH, ICI type and irAE type.

Results

Among 382 patients with irAEs, 255 had IPI+NIVO-induced irAEs and 127 had anti-PD-1-monotherapy-induced irAEs. 268 patients received only corticosteroids; 113 patients additionally received second-line IS. High peak corticosteroid dose was associated with worse PFS (HR 1.47 95%CI 1.00-2.16) and OS (HR 2.17 95%CI 1.49-3.16). Cumulative corticosteroid dose was not associated with PFS or OS (Table). Use of second-line IS was associated with worse PFS (HR 1.57 95%CI 1.04-2.38); for OS, this was the case when correction for cumulative corticosteroid dose (HR 1.57 95%CI 1.06-2.33), but not when correcting for peak corticosteroid dose (HR 1.25 95%CI 0.84-1.85). Subgroup analyses will be presented. Table: 1157P

Association of immunosuppressive irAE management with survival

Conclusions

Our data suggest that use of second-line immunosuppressants and high peak corticosteroid dose are associated with impaired survival among patients requiring IS for irAEs, while there is no association between cumulative corticosteroid dose and survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University Medical Center Utrecht.

Funding

Has not received any funding.

Disclosure

G.A.P. Hospers: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, Roche, Merck Sharp & Dohme, Pfizer, Novartis, Sanofi, Pierre Fabre; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Seerave. M.J.B. Aarts: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, Novartis, Merck Sharp & Dohme, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, Bayer; Financial Interests, Institutional, Research Funding: Merck-Pfizer. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharp & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharp & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editorial Board ESMO Open: ESMO; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board: Kidney Cancer. E. Kapiteijn: Financial Interests, Institutional, Advisory Board: BMS, Novartis, Pierre Fabre, Merck, Delcath, Bayer, Lilly; Financial Interests, Institutional, Coordinating PI: BMS, Pierre Fabre, Delcath. M. Labots: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Janssen-Cilag BV. A.A.M. Van der Veldt: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Pfizer, Novartis, Roche, Eisai, Merck, Pierre Fabre, Ipsen. S. Aspeslagh: Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme, Sanofi, Roche, Bristol Myers Squibb, Pfizer, Ipsen, Galapagos. K.P.M. Suijkerbuijk: Financial Interests, Institutional, Advisory Board: Novartis, BMS, AbbVie, Pierre Fabre, MSD; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Research Grant: Novartis, TigaTx. All other authors have declared no conflicts of interest.