Clinical Characteristics and Outcomes of TFE3-Rearranged/TFEB-Altered Renal Cell Carcinoma with Systemic Therapies, Including Tyrosine Kinase Inhibitors or Immune Checkpoint Inhibitors: An Observational Study

Abstract

Purpose: <i>TFE3</i>-rearranged/<i>TFEB</i>-altered renal cell carcinoma (RCC) is a rare subtype of RCC. Due to its rarity, there is an unmet medical need for effective therapies in advanced settings. The study aims to investigate the clinical and histopathological characteristics of patients with microphthalmia transcription factor family/ transcription factor E (MiTF/TFE) translocation RCC and the clinical outcomes of systemic therapies, including tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs).Materials and Methods: This was a single-center, retrospective study. We identified 32 eligible patients among a total of 37 patients diagnosed with MiTF/TFE translocation RCC between January 2004 and September 2021, and the study included 9 patients who were treated with systemic therapies. We collected data on clinical characteristics, targeted sequencing, and clinical outcomes.Results: The median age of the 32 patients was 45.5 years. Histologically, 26 patients (81.3%) had <i>TFE3</i>-rearranged RCC, and only 1 patient (3.1%) had <i>TFEB</i>-altered RCC. Curative or cytoreductive nephrectomy was performed in all 27 patients (84.4%), and 4 patients (12.6%) were diagnosed with metastatic disease at the time of the initial diagnosis. Nine patients (28.1%) were treated with systemic therapy with TKIs, 2 (6.3%) of whom received simultaneous TKI and ICI treatment. The response to systemic therapy (TKI or ICI) and duration of response ranged from complete response to progressive disease. Excluding 1 patient who was treated with a TKI in the adjuvant setting, the overall response rate in 8 metastatic patients was 50% and the complete response rate was 37.5%. The median follow-up period was 29 months. The median progressionfree survival was 21 months, median overall survival was not achieved, and 2 deaths occurred.Conclusions: Our findings suggest that TKI for treatment for metastatic <i>TFE3</i>-rearranged RCC is efficacious, with an overall response rate of 50% and a median progression-free survival of 21 months.