Clear Cell Histology Associated With Increased Risk of irAEs in Metastatic RCC

Razane El Hajj Chehade, MD

Patients with clear cell histology were associated with an increased risk of developing immune-related adverse effects (irAEs) when treated with frontline immune checkpoint inhibitor–based combinations for metastatic renal cell carcinoma (RCC), according to findings from a retrospective analysis presented at the 2024 Kidney Cancer Research Summit (KCRS).

The findings presented by Razane El Hajj Chehade, MD, and colleagues showed that patients with clear cell RCC had a statistically significant higher risk of developing irAEs vs those with non–clear cell histology (HR, 2.93; 955 CI, 1.05-8.18; P = .04).

The retrospective study included patients with metastatic RCC treated at Dana-Farber Cancer Institute with a first-line regimen containing 2 immune checkpoint inhibitors or an immune checkpoint inhibitor plus a VEGF TKI. Patients were grouped based on the severity of irAEs, with first group including patients who experienced grade 2 or higher irAEs, and the second group featuring patients who had grade 1 irAEs or no irAEs.

“We saw that histology subtype could be a potential risk [factor] for developing irAEs,” El Hajj Chehade said in an interview with OncLive®. She noted that the findings derived thus are preliminary, and the study was limited by a small patient population. There are plans to expand the cohort to better identify risk factors for irAEs in patients with metastatic RCC.

In the interview, El Hajj Chehade discussed the retrospective study of risk factors for irAEs in patients with metastatic RCC, expanded on findings presented at KCRS, and detailed next steps for this research. El Hajj Chehade is a research fellow at Dana-Farber Cancer Institute in Boston, Massachusetts.

OncLive: What was the rationale for evaluating risk factors of irAEs in patients with metastatic RCC treated with immune checkpoint inhibitors?

El Hajj Chehade: Our study focused on identifying the risk factors of irAEs in patients with metastatic RCC treated with immune checkpoint inhibitor[–based] combination therapy, whether that be immuno-oncology [IO] plus IO or IO plus a VEGF [TKI].

We conducted a retrospective study using patients from Dana-Farber Cancer Institute. Patients were divided into groups: those who developed grade 2 or higher irAEs, or those who had [grade 1 or no] irAEs.

What were the key findings from this retrospective study?

After performing univariate and multivariate Cox regression analyses, we saw that [patients with clear cell] histology subtypes could be at potential [higher] risk of developing irAEs. However, we should mention that this was a preliminary analysis.

What are some potential future directions for this research?

We're aiming to improve and increase our cohort in a way that could help clinicians with risk stratification and the management of irAEs [to develop] more personalized treatment of patients.We're planning to increase our cohort in a way that we could validate our findings, as well as develop a model for prediction of irAEs in patients with metastatic RCC.

What other abstracts presented at the 2024 KCRS did you find intriguing.

There were certainly compelling and interesting abstracts and studies [presented] at this meeting. For example, the integration of artificial intelligence [AI] into patient care and treatment is truly transformative in this field. We're seeing AI-based models being used to analyze imaging and lab results [to] predict patient treatment [outcomes] and [inform] clinical care.

Additionally, there was an early phase, pilot study examining implantable microdevices to treat patients with RCC. This is very early phase study assessing in vivo drug efficacy within the tumor microenvironment.

Reference

1. El Hajj Chehade R, Semaan K, Saliby RM, et al. Risk factors of immune related adverse events in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. Presented at: 2024 Kidney Cancer Research Summit; July 11-12, 2024; Boston, MA. Abstract 59.