ASCO 2019: Retrospective Analysis of the Safety and Efficacy of Immune Checkpoint Inhibitors among Patients with Pre-Existing Autoimmune Disorders and Renal Cell Carcinoma or Urothelial Carcinoma

Chicago, IL ( Immune checkpoint inhibitors (CPI) have changed the treatment landscape of both renal cell carcinoma (RCC) and urothelial carcinoma (UC). However, almost all clinical trials involving CPI have restricted the enrollment of patients with pre-existing autoimmune diseases. Prior studies evaluating the use of CPI in other tumor types have shown moderate tolerability in patients with pre-existing autoimmune disorders (ADs).  For example, in a study of ipilimumab in metastatic melanoma patients (n=12) with ADs, 6 patients (50%) had symptomatic worsening or flares of their AD, all of which resolved with short courses of steroids.1  In another larger study including patients with melanoma (n=36), non-small cell lung cancer (n=6), and others (n=3), 24% (11/45) of patients had an AD exacerbation.2 In this study, which included patients from a prospective registry of patients with grade 2 ≥ immune-related adverse events, the overall survival (OS), and objective response rates (ORRs) were no different between patients who had AD and those without. In patients with mRCC and mUC, it is unknown if CPI therapy is safe for patients with AD. This abstract provides a retrospective analysis of the safety and efficacy of immune checkpoint inhibitors in our target population.

This abstract provides data on 103 patients with a variety of different ADs such as psoriasis (22%), thyroiditis (20%), rheumatoid arthritis (13%), polymyalgia rheumatica (8%), inflammatory bowel disease (6%), multiple sclerosis (3%) and lupus (3%) who were treated with CPI in the first or second line setting.
ASCO 2019 fig 1 AD at baseline

57 patients had RCC and 46 patients had UC and their baseline characteristics are shown below.
ASCO 2019 table1 clinicodemographics

Prior to initiation of CPI therapy, 35% of patients had clinically active AD. 37% of patients experienced an exacerbation of their AD, most commonly arthritis and rash. Immune-related AEs unrelated to their ADs occurred in 36% of patients as well including colitis, rash, hypothyroidism, and nephritis.

At the time of data cutoff, 16% of patients had discontinued CPI for toxicity. The ORR was 31% for RCC and 35% for UC, with a 1-year overall survival (OS) of 74% for RCC and 60% for UC.
ASCO 2019 table2 efficacy outcomes

This study sheds light on an important question for our patients with ADs and RCC/UC. While the study is limited by its size, this study shows that the rate of grade 3/4 toxicity amongst patients with ADs appears not too dissimilar than what was reported in where 19% of patients had a Grade 3/4 treatment-related adverse event. In this study, less than 10% of patients required discontinuation of therapy due to AD exacerbation. After careful counseling and control of preexisting ADs, CPIs may be safely given to patients with ADs.
ASCO 2019 fig 3 AD exacerbations

Presented by: Nieves Martinez Chanza, MD, Jules Bordet Institute, Brussels, Belgium

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu, at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

  1. Johnson DB, Khushalani NI, Puzanov I, et al. Ipilimumab in metastatic melanoma patients with pre-existing autoimmune disorders. American Society of Clinical Oncology; 2015.
  2. Danlos F-X, Voisin A-L, Dyevre V, et al. Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease. European Journal of Cancer 2018;91:21-9.