Immune-mediated toxicities (irAEs) in immune checkpoint inhibitor (ICI) therapy in various combinations: A real-world sample.

Abstract

e23376 Background: ICI either alone or in combination with other ICI, tyrosine kinase Inhibitors (TKI), or chemotherapy (CTX) are standard of care for many cancer types. We studied rates of irAEs in a diverse, real-world cohort treated with ICI alone and in various combinations. Methods: We analyzed a real-world clinical dataset of all patients (pts) treated with ICI within the MedStar Health system from 2011-2020. Data regarding treatment regimens and irAEs were obtained from a previously created and curated GU Immunotherapy registry. Initial ICI regimens were subdivided into ICI monotherapy (Mono), ICI+ICI, ICI+CTX, and ICI+TKI. Results: 1927 pts were analyzed, 44.1% female (n = 850), 32.5% African American (n = 626), 56.6% White (n = 1090), average age 65 (16-95). Compared to Mono, rates of most irAEs including rash (32.6% vs 14.4%, p = 0.0001), hepatitis (26.4% vs 6.5%, p = 0.0001), and colitis (16.7% vs 7.0%, p = 0.0001) were significantly higher with ICI+ICI. The ICI+ICI group was comprised of majority melanoma (57.3%) pts. Pneumonitis was higher with ICI+CTX (9.6% vs 5.5%, p = 0.0074) and endocrine irAEs were more common in ICI+TKI (36.1% vs 10.4%, p = 0.0001), especially hypothyroidism (27.8% vs 7.6%, p = 0.0001). Pneumonitis (21.0% vs 5.5%, p = 0.0001) and overall toxicity (65.6% vs 43.3%, p = 0.0001) was higher in durvalumab compared with other Mono agents. The durvalumab group was comprised of pts with lung cancer (98.3%) and a smoking history (100%). Rates of thyroid toxicity (7.3% vs 8.7 %, p = 0.4228) and rash (11.3% vs 14.4%, p = 0.2008) were numerically lower in the ICI+CTX group. Within a lung cancer subgroup, thyroid toxicity was still lower in ICI+CTX (6.5% vs 10.1%, p = 0.0954); however, rash was slightly higher (12.9% vs 11.7%, p = 0.6322). Conclusions: Our results show variability in incidence of toxicity in pts receiving ICI Mono compared with various ICI combinations in a large, diverse, real-world sample representative of a more general pt population. We highlight the potential for enhancing irAEs in combination regimens of multiple ICI agents and ICI combined with TKIs. We also highlight a unique aspect of ICI+CTX where, there is a trend toward lower irAEs suggesting less immune activation with such regimens. Further, the heterogeneity in irAEs observed from various treatment regimens appear to be heavily influenced by the comorbidities common to distinct cancer types. Thyroid Colitis Pneumonitis Hepatitis Rash Mono 119/1363 (8.7%) 96/1363 (7.0%) 75/1363 (5.5%) 88/1363 (6.5%) 192/1363 (14.4%) ICI+ICI 48/227 (21.1%) 38/227 (16.7%) 11/227 (4.8%) 60/227 (26.4%) 74/227 (32.6%) p=0.0001 p=0.0001 p=0.6855 p=0.0001 p=0.0001 ICI+CTX 22/301 (7.3%) 27/301 (9.0%) 29/301 (9.6%) 22/301 (7.3%) 34/301 (11.3%) p=0.4228 p=0.2475 0.0074 p=0.5900 p=0.2008 ICI+TKI 11/36 (30.6%) 4/36 (11.1%) 0/36 (0%) 4/36 (11.1%) 2/36 (8.3%) p=0.0001 p=0.3497 p=0.1480 p=0.2661 p=0.1438