irAE in CKD [2023 Slides] - Dalia Kaakour, MD - MOASC

This study by Dalia Kaakour, MD, MPH, investigates immune-related adverse events (irAEs) in patients with solid tumors and advanced chronic kidney disease (CKD) undergoing checkpoint inhibitor (CPI) treatment, revealing comparable irAE incidence.


Presented By: Dalia Kaakour, MD - University of California, Irvine 

Date: Aug 12, 2023

In the realm of oncology and immunotherapy, the investigation into the safety and efficacy of immune checkpoint inhibitors (CPIs) takes a step forward with an insightful study by Dr. Dalia Kaakour, MD, MPH, from the University of California, Irvine's Department of Medicine Division of Hematology and Oncology Fellowship Program. With an absence of any disclosures, this study delves into the realm of immune-related adverse events (irAEs) in patients afflicted by both solid tumors and advanced chronic kidney disease (CKD) who are undergoing treatment with CPIs.

Traditionally, clinical trials involving CPIs have often excluded patients grappling with advanced CKD and end-stage renal disease (ESRD). However, this study seeks to bridge this gap in knowledge, as it examines the safety and potential adverse effects of CPIs in this specific subset of patients. Initial observations from the available data have indicated that the incidence of irAEs among patients with advanced CKD/ESRD undergoing CPI treatment is comparable to that of individuals with normal or mildly impaired renal function. Importantly, CPIs do not necessitate modifications based on dialysis due to their unique molecular size, and they don't require renal dosing, thereby adding to the complexity of their interaction in patients with CKD.

A notable aspect of this research is the inclusion of multiple case reports and case series involving patients with end-stage renal disease on hemodialysis who are concurrently managing solid tumor malignancies with CPI therapies. The study's cohort comprises a total of 98 patients, featuring a spectrum of tumor types including renal cell carcinoma (32), urothelial carcinoma (23), melanoma (16), and lung cancer (6). The specific CPIs employed were Nivolumab (38), Pembrolizumab (26), and Atezolizumab (8), showcasing the diversity of treatment regimens in this context.

Within this patient cohort, 48 irAEs were identified, further classified into different grades of severity. Impressively, 33 of these irAEs were categorized as grade 1-2, indicating milder adverse events, while 15 fell into the grade 3-4 spectrum, representing more serious complications. These irAEs encompassed a range of manifestations, such as hematologic abnormalities (12), dermatologic issues (8), pneumonitis (5), endocrine disorders (4), hepatitis (3), gastrointestinal distress or diarrhea (2), encephalitis (1), and myocarditis (1). This diversity underscores the complexity of the immune system's response in patients with CKD under the influence of CPIs.

The methods employed for this study included an examination of results from a cohort of 32 patients. Among the intriguing findings were the most common types of irAEs encountered. A significant proportion (78.3%) of these irAEs manifested as grade 1-2 events, indicating the tolerability of the CPI treatments to a certain extent. However, a noteworthy 21.7% of the irAEs escalated to grades 3-5, signaling the potential for more serious adverse outcomes. Specifically, colitis emerged as the most prevalent irAE (26.1%), followed by endocrinopathies (17.4%) and dermatologic issues (17.4%).

In the light of these findings, several compelling conclusions were drawn. Foremost, the safety of CPIs in patients suffering from solid tumors and advanced CKD has not undergone comprehensive evaluation, emphasizing the importance of this study's contribution. The similarity in the incidence and types of irAEs between advanced CKD patients and those with normal or mildly impaired renal function suggests potential parallels in immune response. However, the need for more prospective data in this particular patient population, particularly those with CKD5/ESRD, remains evident. The quest for deeper insights continues as researchers and clinicians work collaboratively to enhance the understanding of CPI treatment in patients grappling with both solid tumors and advanced CKD.