Safety of PD-1/PD-L1 Inhibitors in Patients With NSCLC and Preexisting Autoimmune Disorders


Key Points

  • An autoimmune disease flare occurred in 23% of patients, with systemic corticosteroid treatment required in a minority.
  • Immune-related adverse events occurred in 38% of patients, with 26% of such events being grade 3 or 4. 

In a study reported in the Journal of Clinical Oncology, Leonardi et al found that programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy in patients with non–small cell lung cancer (NSCLC) and autoimmune disorders worsened such disorders in a minority of patients and was not associated with an increased frequency of new immune-related adverse events. Patients with NSCLC and concurrent autoimmune disease have been excluded from immunotherapy clinical trials.

The study involved a retrospective review of clinicopathologic data from 56 patients with advanced NSCLC and a history of autoimmune disease who received monotherapy with a PD-1 or PD-L1 inhibitor at 5 U.S. sites (Dana-Farber Cancer Institute, Massachusetts General Hospital, The University of Texas MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, and the University of California Davis Comprehensive Cancer Center). Qualifying autoimmune disorders included rheumatologic, neurologic, endocrine, gastrointestinal, and dermatologic conditions.

Immune-Related Adverse Effects

At the time of treatment initiation, 18% of patients had active autoimmune disease symptoms and 20% were receiving immunomodulatory treatment for their condition. Overall, a total of 55% of patients developed an autoimmune disease flare (23%) and/or an immune-related adverse event.

Worsening of the preexisting condition in 13 patients resulted in the need for systemic corticosteroid treatment in 4. Among new immune-related adverse events in 21 patients (38%), 74% were grade 1 or 2 and 26% were grade 3 or 4; in total, 8 patients required systemic corticosteroids for management of the adverse events. Immune-related adverse events led to permanent discontinuation of treatment in 8 patients (14%). The overall response rate to PD-1/PD-L1 inhibitor therapy in the 56 patients was 22%.

The investigators concluded, “In patients with NSCLC with [autoimmune disease] treated with a [PD-1 or PD-L1] inhibitor, exacerbation of [autoimmune disease] occurred in a minority of patients. The incidence of [immune-related adverse events] was similar to reported rates in clinical trials where patients with [autoimmune disease] were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.”

The study was supported by the Kaplan Research Fund and Jeni Fund, a Memorial Sloan Kettering Cancer Center support grant, an American Cancer Society grant, and others.

Mark M. Awad, MD, PhD, of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.