Safety of Programmed Death–1 Pathway Inhibitors Among Patients With Non–Small-Cell Lung Cancer and Preexisting Autoimmune Disorders

Abstract

Purpose Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non-small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown. Methods As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions. Results We identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%. Conclusion In patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.

Reply

“…First, the authors suggested classifying preexisting autoimmune diseases according to systems in order to assess if rheumatic disorders were more likely to flare with ICIs. Such trends have been reported in other studies , with the limitation that the highest percentage of preexisting autoimmune diseases in the cohorts studied were rheumatic disorders (n = 27 [52%] in ref. 1 and n = 25 [45%] in ref.…”

“…For these reasons, we consider it more meaningful to classify the diseases according to the diagnosis, with a larger sample size, even if a classification by system might add clinical value. Interestingly, more flares were reported in the psoriasis group in our cohort, and 50% of patients with inflammatory bowel disease (IBD) experienced a flare, compared to lower flare frequencies reported in other retrospective cohorts . IBD represented a larger sample size in our cohort.…”

Clinical Outcomes of Patients with Advanced Cancer and Pre-Existing Autoimmune Diseases Treated with Anti-Programmed Death-1 Immunotherapy: A Real-World Transverse Study

“…In our study, the incidence of irAEs of any grade and G3/G4 irAEs among patients with pre‐existing AIDs were 65.9% and 9.4%, respectively. The rates of irAEs of any grade seem worse than those observed by Menzies et al (29%), Leonardi et al (38%), and Danlos et al (44.4%), although G3/G4 events are quite comparable (10% of G3, and 10.7%, respectively—not reported by Danlos et al) . Forty patients (47.1%) among those with pre‐existing AIDs developed a flare of the underlying disease; similarly, in the studies of Leonardi et al (23%) and Danlos et al (24.4%), the flare rates were lower than the incidence of irAEs overall, whereas in the study of Menzies et al, it was higher (38%) than the “conventional” irAEs rate.…”

Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis

“…A history of autoimmunity has previously been thought to confer a higher risk of toxicity to PD‐1 inhibitors; therefore, patients with such a history have been excluded from clinical trials with these drugs. Existing retrospective data suggests that PD‐1 inhibitors can safely be used in patients with a history of AD and although flares of the pre‐existing AD are common, they are often of mild severity and manageable . Four patients (8%) in the present cohort had a history of pre‐existent AD, and three of these four patients experienced either a flare of their underlying AD or another IrAE with PD‐1 inhibitor therapy.…”