1138P - Delayed immune-related adverse events (irAEs) on anti-PD1-based therapy

Background

IrAEs typically occur within 4 months of starting anti-PD1-based therapy (anti-PD1 +/- anti-CTLA4), but there are isolated reports of delayed irAEs (onset >12 months after commencement). This study describes the incidence, nature and management of delayed irAE in melanoma patients (pts).

Methods

Pts from 20 centres with delayed irAEs were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma pts treated with anti-PD1-based therapy and surviving >1yr. irAE onset, clinical features, management and outcomes were examined.

Results

122 pts developed a total of 144 delayed irAEs (23 after initial combination anti-PD-1 with anti-CTLA-4); with an estimated incidence of 5.7% (95% CI 4.3-7.3, 57/999 pts at sites with complete data). The median duration of therapy was 17.7 months (range 0.7-56.0), and median onset of delayed irAE was 16.3 months (range 12.0-53.2). 74% (90 pts) were on anti-PD1 at irAE onset, 12% (15 pts) were <3 months from last dose, 14% (17 pts) were >3 months from last dose of anti-PD1. The most common delayed irAEs were colitis, rash and pneumonitis (Table); 16% (19 pts) had multiple delayed irAEs, 39% (56 irAEs) were ≥G3. Steroids were required in 66% (81 pts), as well as an additional immunosuppressive agent in 23% (28 pts). There were 2 irAE-related deaths; encephalitis with onset during anti-PD1 and a multiple organ-irAE (colon, liver, kidney, lung and haem irAE) with onset 11.4 months after ceasing anti-PD1. Early irAEs (<12 months) had also occurred in 60% (73 pts), affecting a different organ to delayed irAEs in 86% (63 pts). Table: 1138P

Conclusions

Delayed irAEs occur in a small but relevant subset of pts, are often different to previous irAE, high grade, difficult to manage and can lead to death. Delayed irAEs mostly occur in pts still receiving anti-PD1, such that the risks of irAE need to be weighed against the benefits of continuing treatment in responding pts beyond 1 year, however pts who stopped treatment remained at risk for developing delayed irAE.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C.N. Owen: Non-remunerated activity/ies: MSD. X. Bai: Travel/Accommodation/Expenses, Merit award: BMS. W. Xu: Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono; Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: Novartis. S.J. Welsh: Travel/Accommodation/Expenses: Ipsen. S. Sandhu: Honoraria (self): Merck Sharp and Dohme; Honoraria (self): BMS; Honoraria (self): Amgen; Honoraria (self): Endocyte; Honoraria (self): AstraZeneca; Honoraria (self): Roche. J. Mangana: Advisory/Consultancy: Merck-Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck-Sharp-Dohme; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: Ultrasun; Travel/Accommodation/Expenses: L'Oreal. J.L. McQuade: Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck. P.A. Ascierto: Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Roche-Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (self): Array; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pierre fabre; Advisory/Consultancy: Incyte; Advisory/Consultancy: Newlinks genetics; Advisory/Consultancy: Genmab; Advisory/Consultancy: Medlmmune; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Sindax; Advisory/Consultancy: Sun pharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Idera; Advisory/Consultancy: Ultimovacs; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Immunocore; Advisory/Consultancy: 4SC; Shareholder/Stockholder/Stock options: PrimeVax; Leadership role: Fondanzione Melanoma Onlus; Leadership role: Campania Society if ImmunoTherapy of Cancer; Leadership role: Society of Melanoma Research; Leadership role: Cancer Development Drug Forum; Leadership role: Society of ImmunoTherapy of Cancer; Advisory/Consultancy: Alkermes; Advisory/Consultancy: Italfarmaco; Advisory/Consultancy: Nektar. L. Zimmer: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Sunpharma. D.B. Johnson: Advisory/Consultancy: Array Biopharma; Advisory/Consultancy, Research grant/Funding (self): BMS; Research grant/Funding (self): Incyte; Advisory/Consultancy: Jansen; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Leadership role, melanoma scientific committee chair: ASCO; Leadership role, Melanoma committee: NCCN. C. Lebbé: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Honoraria (institution): MSD; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Pierre Fabre; Honoraria (self): Merck Serono; Honoraria (self): Sanofi; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: Roche. A.M. Menzies: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.