Risk of immune-related adverse events (irAE) with immune checkpoint inhibitors (ICI) in patients (pts) with family history (FH) of autoimmune disease (AID).

Authors

null

Piyush Grover

Melanoma Institute Australia, The University of Sydney, Sydney, Australia

Piyush Grover , Isabel Li , Alexander M. Menzies , Georgina V. Long

Organizations

Melanoma Institute Australia, The University of Sydney, Sydney, Australia, Melanoma Institute Australia, Sydney, Australia, Melanoma Institute Australia, Wollstonecraft, NSW, Australia, The University of Sydney, Sydney, NSW, Australia

Research Funding

No funding received
None.

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.

Baseline characteristics.

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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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics—Immunotherapy

Sub Track

Other IO-Related Topics

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 2648)

DOI

10.1200/JCO.2023.41.16_suppl.2648

Abstract #

2648

Poster Bd #

490

Abstract Disclosures