PD-1 Inhibition Minimally Affects Cisplatin-Induced Toxicities in a Murine Model

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Abstract

Immune checkpoint inhibition used in combination with standard cisplatin-based chemotherapy regimens is currently under evaluation in clinical trials for head and neck squamous cell carcinoma (HNSCC). The impact of anti–PD-1 therapy on cisplatin-induced ototoxicity and nephrotoxicity has not been established. Here we use a murine model of cisplatin-induced hearing loss to investigate the impact of anti–PD-1 immunotherapy on auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), serum creatinine, and hair cell and renal histology. We demonstrate only mild worsening of DPOAEs at 14.4 and 16 kHz as well as a mild increase in serum creatinine. Renal and hair cell histology as well as ABR measures were unchanged by PD-1 inhibition. Thus, our data suggest that the use of PD-1 inhibition in conjunction with cisplatin results in toxicities that are similar to those of cisplatin alone.

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