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Remarkable Response to Immunotherapy and VEGFR Inhibitor in Xp11 Translocation Renal Cell Carcinoma in a 17-Year-Old
Piyarat Limpawittayakul1, Narongchai Teerayathanakul2
1Department of Medical Oncology, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand, cra.ac.th.
Background:
Xp11 translocation renal cell carcinoma (tRCC) is a rare and aggressive renal cancer characterized by gene fusion involving TFE3. It accounts for < 5% of renal cancers and shows variable responses to conventional antivascular endothelial growth factor therapies. Optimal treatment strategies for metastatic cases have not been determined.
Objective:
To report the clinical presentation, molecular diagnosis, and therapeutic response of an adolescent patient with metastatic Xp11 tRCC treated with pembrolizumab and lenvatinib.
Methods:
A 17-year-old female presented with a large left renal mass, gross hematuria, extensive metastases to the supraclavicular, mediastinal, and intra-abdominal lymph nodes, and pleural nodules. Immunohistochemistry confirmed transcription factor E3 (TFE3) positivity, and next-generation sequencing identified an ASPSCR1-TFE3 fusion. Following renal embolization for local control, the patient received systemic therapy (pembrolizumab at 200 mg/dose given every 3 weeks and lenvatinib at 10 mg-20 mg/day).
Results:
The patient showed rapid clinical improvement, with her Eastern Cooperative Oncology Group Performance Status Scale grade improving from 3 to 1 after the initial cycles. CT imaging after the sixth cycle demonstrated a marked reduction in the size of the primary tumor and in the sizes and numbers of metastatic lesions, involved lymph nodes, and pleural nodules. The patient recovered to normal well-being.
Conclusion:
Pembrolizumab combined with lenvatinib showed significant antitumor activity in an adolescent with advanced ASPSCR1-TFE3 fusion Xp11 tRCC. These findings support the utility of molecular profiling of renal tumors in young adults and suggest that this combination is an effective treatment option for this subtype of renal cancer.
Insights
This study shows that a combination of pembrolizumab and lenvatinib effectively treated metastatic Xp11 translocation renal cell carcinoma (tRCC) in an adolescent. Molecular profiling is crucial for identifying this rare cancer subtype in young adults.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Xp11 translocation renal cell carcinoma (tRCC) is a rare, aggressive cancer driven by TFE3 gene fusions.
- It comprises less than 5% of renal cancers and responds variably to standard therapies.
- Optimal treatment for metastatic tRCC remains undetermined.
Purpose of the Study:
- To detail the clinical presentation, molecular diagnosis, and treatment response in an adolescent with metastatic Xp11 tRCC.
- To evaluate the efficacy of pembrolizumab and lenvatinib in this patient population.
Main Methods:
- A 17-year-old female diagnosed with metastatic Xp11 tRCC.
- Molecular confirmation via immunohistochemistry for TFE3 and next-generation sequencing for ASPSCR1-TFE3 fusion.
- Treatment with renal embolization, followed by pembrolizumab and lenvatinib.
Main Results:
- The patient experienced rapid clinical improvement, with improved performance status.
- CT scans showed significant reduction in primary tumor and metastatic lesions.
- The patient achieved a return to normal well-being.
Conclusions:
- Pembrolizumab and lenvatinib demonstrated significant antitumor activity in advanced ASPSCR1-TFE3 fusion Xp11 tRCC.
- Supports molecular profiling for young adults with renal tumors.
- Suggests this combination therapy is effective for this rare renal cancer subtype.
