Immune related kidney toxicity, management, and outcomes in ICI treated patients with advanced or metastatic cancers.

2601 Background: The impact of kidney immune-related adverse events (KirAEs) and their management (mgmt) on clinical outcomes in patients receiving immune checkpoint inhibitors (ICI) has not been fully examined. We aimed to evaluate the association between KirAEs, their mgmt, and progression-free survival (PFS) and overall survival (OS) in ICI-treated cancer patients. Methods: Data were drawn from the Flatiron Health Research Database, an EHR-based database representing 280+ U.S. oncology practices. Adults with advanced non-small cell lung cancer (aNSCLC), advanced melanoma (aMel), or metastatic renal cell carcinoma (mRCC) who initiated ICI between 1/1/16 - 12/31/20 were included and followed from ICI initiation to death, loss to follow-up, or end of the study period (12/31/21). CTCAE Grade 2 or higher KirAEs and mgmt actions (immunosuppression using corticosteroids or other immunosuppressants, ICI-regimen holds, ICI-regimen discontinuations) and hospitalizations were curated from unstructured data. Cox regression was used to evaluate the association between KirAEs, their mgmt (both as time-varying covariates) and PFS and OS adjusting for baseline characteristics such as line of therapy and corticosteroid use. The earliest KirAE per patient was examined in survival analyses. Results: The study included 513 aNSCLC, 463 aMel, and 451 mRCC patients. For aNSCLC, aMel, and mRCC, respectively, 21.1%, 29.6%, and 33.9% experienced at least one KirAE, with a median time to onset of 70, 84, and 128 days. Nephritis ranged from 2.1% of KirAEs in aNSCLC to 4.6% in aMel. Elevated creatinine was the most common KirAE (23.6% in mRCC to 29.1% in aNSCLC), followed by acute kidney injury (20.5% in mRCC to 28.4% in aNSCLC). Immunosuppression was used to treat KirAEs in 67.6%, 80.3%, and 67.3% of aNSCLC, aMel, and mRCC patients with KirAEs. In aNSCLC, aMel, and mRCC, respectively, median OS was 17.1, 58.6, and 33.7 months, median PFS was 7.8, 8.9, and 9.5 months, and patients with KirAEs had longer PFS than those without KirAEs [HR (95%CI): 0.65 (0.51-0.83); 0.74 (0.57-0.97); 0.67 (0.53-0.84)]. In aNSCLC, KirAEs were associated with shorter OS [1.31 (0.98-1.74); P = 0.06]. In all cancers, KirAEs that occurred during hospitalization or led to hospitalization were associated with shorter OS (HR≥2.84; P < 0.02). KirAE mgmt was not associated with OS or PFS. Conclusions: Results suggest that while KirAEs might indicate an intensified immune response, their management and impact on survival vary across cancer types and call for cancer-specific strategies for early identification and management of KirAEs in the ambulatory care setting.