Immune checkpoint inhibitors (ICI) are an important treatment for metastatic renal cell carcinoma (mRCC). These agents may cause immune-related adverse events (irAEs) and the relationship between irAEs and outcomes is poorly understood. We investigated the association between irAEs and clinical outcomes in ICI-treated mRCC patients.
We performed a retrospective study of 200 ICI-treated mRCC patients at Winship Cancer Institute from 2015-2020. Data on irAEs were collected from clinic notes and laboratory values and grades were determined using common terminology criteria in adverse events (CTCAE) version 5.0. The association with overall survival (OS) and progression-free survival (PFS) was modeled by Cox proportional hazards model. Logistic regression models were used to define odds ratios for clinical benefit (CB). Landmark analysis and extended Cox models were used to mitigate lead-time bias by treating irAEs as a time-varying covariate.
Most patients (71.0%) were males and one-third of patients (33.0%) experienced ≥1 irAE, most commonly involving the endocrine glands (13.0%), gastrointestinal tract (10.5%), or skin (10.0%). Patients who experienced irAEs had significantly longer OS (HR=0.52, p=0.013), higher chance of CB (OR=2.10, p=0.023) and showed a trend towards longer PFS (HR=0.71, p=0.065) in multivariate analysis. Patients who had endocrine irAEs, particularly thyroid irAEs, had significantly longer OS, PFS, and higher chance of CB. In 14-week landmark analysis, irAEs were significantly associated with prolonged OS (p=0.045). Patients who experienced irAEs had significantly longer median OS (44.5 versus 18.2 months, p=0.005) and PFS (7.5 versus 3.6 months, p=0.003) without landmark compared to patients who did not.
We found that ICI-treated mRCC patients who experienced irAEs, particularly thyroid irAEs, had significantly improved clinical outcomes compared to patients who did not have irAEs. This suggests that irAEs may be effective clinical biomarkers in ICI-treated mRCC patients. Future, prospective studies are warranted to validate these findings.
We found that early onset immune-related adverse events (irAEs) are associated with significantly improved clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immune checkpoint inhibitors (ICI). In our site-specific irAE analysis, endocrine irAEs, particularly thyroid irAEs, were significantly associated with improved clinical outcomes. These results have implications for practicing medical oncologists given the increasing utilization of ICIs for the treatment of mRCC. Importantly, these results suggest that early irAEs and thyroid irAEs at any time on treatment with ICIs may be clinical biomarkers of clinical outcomes in mRCC patients treated with ICIs.
The oncologist. 2021 Jun 22 [Epub ahead of print]
Dylan J Martini, Subir Goyal, Yuan Liu, Sean T Evans, T Anders Olsen, Katherine Case, Benjamin L Magod, Jacqueline T Brown, Lauren Yantorni, Greta Anne Russler, Sarah Caulfield, Jamie M Goldman, Bassel Nazha, Wayne B Harris, Haydn T Kissick, Viraj A Master, Omer Kucuk, Bradley C Carthon, Mehmet Asim Bilen
Massachusetts General Hospital, Department of Medicine, Boston, MA, USA., Departments of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA., Winship Cancer Institute of Emory University, Atlanta, GA, USA., Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA., Department of Urology, Emory University School of Medicine, Atlanta, GA, USA.