Melanoma Institute Australia, The University of Sydney, Sydney, Australia
Piyush Grover , Isabel Li , Alexander M. Menzies , Georgina V. Long
Background: Pts with personal history (PH) of AID are at increased risk of irAE following ICI. Risk of irAE in pts with FH of AID is unknown. Methods: In this retrospective cohort study, consecutive pts were recruited from 2 Australian melanoma cancer centers. Pts who received anti-PD-1 (PD1) based ICI with FH of AID were eligible. Pts with PH of AID were excluded. Toxicity data (CTCAE v5.0) was obtained and stratified by FH of AID (first/second/third degree relative). Descriptive statistics and Fisher’s Exact test were used for analysis. Results: 396 melanoma cases were screened, of which 44 (11.1%) were eligible for inclusion. Baseline characteristics are summarized. 57 irAE occurred in 44 pts. The most common irAE were dermatological (n=11; 19.3%), colitis (n=8; 14.0%), endocrinopathies (n=8; 14.0%), hepatitis (n=7; 12.3%) and arthritis (n=7; 12.3%). Among 57 irAE, frequency of Grade 1,2,3 and 4 irAE was 16 (28.1%), 26 (45.6%), 12 (21.0%) and 3 (5.3%) respectively. Corticosteroids were used for 31 (54.4%) irAE. Hospital admission for management of irAE occurred in 11 pts (25.0%). ICI was discontinued in 20 pts (45.5%) due to irAE. In pts with irAE, FH of that irAE/AID was present in 6 pts (13.6%) (n= 2 x arthritis, n= 2 x psoriasis, n= 1 x Crohn’s disease, n= 1 x Grave’s disease), and 4 of these patients had a first-degree relative with an AID. 3/6 pts had ICI ceased due to an irAE (peak toxicity Grade was 3) and 4/6 pts had RECIST response. There was no association in development of irAE between patients with FH of AID in a first-degree relative and those with FH of AID in second or third degree relative (p=0.17). Rate of irAE in pts with FH of AID was not statistically higher to that reported in registration trials of similar regimens (p=0.40). Conclusions: FH of AID is common in melanoma pts and was not associated with higher rate or morbidity of irAE. FH AID should be routinely collected, and larger scale studies need to be performed.
N = 44 | |
---|---|
Age, median (years) (IQR) | 60.5 (45.7-69.0) |
Sex, n (%) Male Female | 18 (40.9) 26 (59.1) |
Melanoma sub-type, n (%) Cutaneous Acral/mucosal Unknown | 35 (79.5) 4 (9.1) 5 (11.4) |
Treatment setting, n (%) Adjuvant Advanced | 24 (54.5) 20 (45.5) |
ECOG PS, n (%) 0-1 | 44 (100) |
LDH pre-ICI, n (%) Normal Elevated Unknown | 32 (72.7) 10 (22.7) 2 (4.6) |
Mutation, n (%) Triple wildtype BRAF V600 Other | 21 (47.7) 12 (27.3) 11 (25.0) |
FH AID, n (%) First degree only Second degree only Third degree only First + second degree Second + third degree First, second and third degree | 27 (61.4) 8 (18.2) 1 (2.3) 5 (11.3) 2 (4.5) 1 (2.3) |
Type of AID, n (%) Rheumatoid arthritis Other multi system rheumatological Psoriasis Inflammatory bowel disease Coeliac disease Type 1 diabetes mellitus Grave’s disease Other | N = 56 16 (28.6) 5 (8.9) 3 (5.3) 8 (14.3) 8 (14.3) 6 (10.7) 8 (14.3) 2 (3.6) |
ICI, n (%) PD1 monotherapy PD1 + Ipilimumab PD1 ± other ICI | 12 (27.3) 12 (27.3) 20 (45.4) |
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