A recent study investigated the effectiveness of a combination treatment using cabozantinib and nivolumab for advanced, non clear cell kidney cancer. The researchers found that this combination was active in patients with non-clear cell renal cell carcinoma (RCC), especially those with papillary histology variants. 

The study enrolled 47 patients who had not received much prior treatment. They were divided into two groups: one with papillary, unclassified, and translocation-associated RCC, and the other with chromophobe RCC. The patients received cabozantinib and nivolumab as part of their treatment.

The results showed that nearly half of the patients in the first cohort had a partial response to the treatment, and stable disease was observed in others. However, no objective responses were seen in the patients with chromophobe RCC.

The study also analyzed the genetic mutations in the patients and found that certain mutations were associated with better responses to the treatment. Notably, patients with NF2 or FH mutations had a higher rate of objective responses.

The combination treatment was generally well-tolerated, although some patients experienced side effects such as fatigue, skin reactions, and diarrhea. A small number of patients had more severe adverse events, leading to discontinuation of the treatment in some cases.

In conclusion, the combination of cabozantinib and nivolumab showed promising effectiveness in treating non-clear cell RCC, particularly those with papillary features. However, its efficacy was limited in patients with chromophobe RCC. Further research is needed to understand the role of genetic factors in predicting the response to this treatment.

For individuals with hereditary leiomyomatosis and renal cell carcinoma (HLRCC), which is associated with FH mutations, this study suggests that the combination treatment may be beneficial. 

References:

1.) https://ascopubs.org/doi/abs/10.1200/JCO.21.01944?journalCode=jco

2.) https://ascopost.com/news/march-2022/cabozantinib-plus-nivolumab-in-advanced-non-clear-cell-renal-cell-carcinoma/