Immunotherapy-Related Toxicities and Renal Cell Carcinoma

Abstract

Research Question: What are the barriers to recognizing and diagnosing immunotherapy related toxicities and how does prompt initiation of steroids improve patient outcomes? In adult patients with advanced stage renal cell carcinoma, does timely recognition of immunotherapy toxicity including both PDL-1 and PDL inhibitors as well as CTLA-4 inhibitors (ex. ipilimumab, pembrolizumab, and nivolumab) and time to steroid treatment initiation lead to a better outcome? We will explore the barriers to both early toxicity recognition and beginning proper steroid treatment.

Background and Significance: According to National Comprehensive Cancer Network (NCCN guidelines), ¿Corticosteroids are the mainstay of treatment for most high-grade immunotherapy-related adverse events (irAE) and short-term use of corticosteroids to treat irAEs has not been shown to reduce anti- tumor efficacy.¿ (NCCN version 2.2019) Immunotherapy is used to boost one¿s immune system response to target cancer cells. Prompt holding of these agents and initiation of steroids cause suppression of the immune therapy related toxicities to alleviate conditions. Our study focused on renal cell carcinoma, and the immunotherapies ipilimumab, pembrolizumab, and nivolumab to identify barriers in the onset of steroid treatment. Some barriers for starting steroids are fear of worsening hyperglycemia in diabetics, fear of counteracting immunotherapy response, delay of re-initiation of therapy once on steroids, a long taper over 4-6 weeks, etc.

Materials and Methods: Under the guidance of my mentor, Dr. Ina Patel, I will conduct a retrospective study analyzing adult patients (ages 18-75) being treated for renal cell carcinoma at UT Southwestern Medical Center and Moncrief Cancer Institute (MCI) from 2016-2021. This will be done using the Epic electronic medical record database from the clinic both in Dallas and Fort Worth locations. Patients will be identified for the study through a chart review, and their immunotherapy medication, possible toxicities, duration of steroid medication, timing of steroid medication after identifying toxicity, overall patient outcome, etc. will be documented. We will record this data, de-identify it and analyze this data with the help of a biostatistician from UT Southwestern Medical Center.

Results: Upon review of 201 patients with renal cell carcinoma (RCC) stage III/IV, the most common toxicity found was colitis (28.4%), followed by transaminitis (9.0%) and pneumonitis (9.0%). The most common methods for identification of toxicities was routine lab work performed before immunotherapy administration (30.4%), check-ins at regularly scheduled appointments (21.7%), and after-hour physician telephone lines (19.6%). Additionally, the average time from irAE identification to steroid administration was 1.45 days. Excluding toxicities found either at office appointments or on routine lab work, the average time to steroids from identification was 3.55 days.

Conclusion: Our study largely revealed that the current practices were successful in helping patients and providers identify irAEs in a timely fashion, leading to quicker steroid administration, and in turn, a sooner return to immunotherapy treatment. This study can be used as a blueprint and expanded to further investigate irAEs in other solid tumors as well as contribute to management of the ever-evolving immunotherapy landscape.