Immune-related adverse events after 2 years in patients with advanced non-small-cell lung cancer receiving extended immune checkpoint inhibitor therapy.
Authors: Elghawy Omar , Barsouk Adam , Sussman Jonathan Henry , Davella Christopher , Singh Aditi Puri , Ciunci Christine Agnes , Robinson Kyle William , Kosteva John A. , Langer Corey J. , Cohen Roger B. , Aggarwal Charu , Marmarelis Melina Elpi , Sun Lova 
Published: June 2024

8551 Background: Immune checkpoint inhibitors (ICIs) have improved survival outcomes in patients (pts) with advanced non–small cell lung cancer (NSCLC). Although pivotal trials stipulated ICI therapy for up to 2 years, many pts in clinical practice continue therapy beyond 2 years. Data on long-term toxicities developing after more than 2 years of ICI treatment are very limited. Methods: A single-institution retrospective analysis including pts who received greater than 2 years of ICI therapy for recurrent/metastatic NSCLC from 01/2012-01/2023 was performed. Patient demographics, disease characteristics, treatment history, toxicities, and outcomes were abstracted from the electronic medical record. Late IRAEs were defined as those occurring more than 2 years after initiation of ICI therapy. IRAEs were graded using CTCAE v5.0 by chart review. Independent sample t-tests and chi-square analyses were used for univariate comparisons. Association of late IRAE with OS and PFS was assessed using extended Cox regression with late IRAE modeled as a time varying covariate. Results: Our cohort consisted of 76 pts who received > 2 years of ICI therapy. Median age at the 2-year time point was 64 (range 40-83); 51 (67.1%) were White; 48 (63.2%) were Female; 66 (86.8%) had ECOG PS 0-1; 66 (88.0%) had non squamous histology. More than half (42/76, 55.3%) had PD-L1 TPS ≥50%, while 18/76 (23.7%) had PD-L1 TPS 1-49%. Median duration of ICI treatment was 41.1 mos (range 26.5- 84.4 mos). Before the 2-year time point, 44 (57.8%) patients had an IRAE; most (38/44, 86.3%) were Grade 1-2; only 11 (26.2%) of these pre-2-year IRAEs required steroids, with the remainder managed with symptomatic support. After 2 years on ICI therapy, 38/76 (50%) pts had a late IRAE, most of whom (23/38, 60.5%) had no evidence of IRAE prior to 2 years. Of the 15/38 pts (39.5%) with a prior IRAE before 2 years, only 3 late IRAEs (20%) involved the same organ system as the pre-2 year IRAE. Late IRAEs were most commonly dermatologic (26.3%), gastrointestinal (21.1%) and musculoskeletal (18.4%). Of the 38 late IRAEs, 7 (18.4%) were grade 1; 21 (55.3%) grade 2; and 10 (26.3%) grade 3. Steroids for late IRAEs were required in 14 (36.8%) pts while 24 pts (63.2%) were managed with supportive care. ICI therapy was discontinued due to late IRAE in 15/38 pts (39.4%). Higher rates of late IRAEs were seen in females (p=0.032), non-white pts (p=0.041), and in pts who had experienced grade > 2 or higher IRAE before 2 years (p=0.020). Late IRAE occurrence was not significantly associated with mPFS (p=0.965) or mOS (p=0.691). Conclusions: Late IRAEs are common in pts with NSCLC treated with ICI therapy beyond 2 years, including in patients with no prior history of IRAE. Females, non-Caucasian patients, and patients with previous high grade IRAEs may be at higher risk for developing late IRAEs. Late IRAEs do not appear to be associated with longer PFS and OS.