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Kosuke Takemura: Hello, everyone. I'm Dr. Kosuke Takemura, a staff urologist at the Japanese Foundation for Cancer Research. I'm so honored to be invited to introduce to the audience of UroToday, our latest paper just published in ESMO Open. In this study, we examine the prognostic significance of the absolute lymphocytes count in patients with metastatic renal cell carcinoma, receiving first-lying combination immunotherapies. Given that lymphocytes are known to be closely linked to the mechanisms of action of IO agents. However, the relevant studies in the field are lacking. We use the IMDC International Metastatic Renal Cell Carcinoma database Consortium in this study, which was founded by Doctors Daniel Heng and Toni Choueiri. I am also one of the IMDC collaborators in charge of the Japanese cohort.

This is a cohort creation. Overall, 966 patients were included in this study who received either IO-IO doublet therapy, or IO-VGF combination therapy. Of them, 195 patients accounting for 20% had a baseline lymphopenia, which was defined in this study. The lymphocytes count less than 1000 cells per microliter on initiation of systemic therapy. Lymphopenia was significantly associated with unfavorable oncologic outcomes, such as show to time-to-next treatment as shown in the upper panel, medium value 10 months versus 24 months, as well as the shorter overall survival, as shown in the lower panel, the medium value 30 months versus 48 months. On multi-variable analysis, lymphopenia was significantly and independently associated with the shortest of all survival with a hazard ratio of 1.68. When we looked at C index, which is an indicator of model accuracy, incorporation of lymphopenia into the IMDC criteria improved its C index from 0.688 to 0.707. Notably, a greater improvement in C index was observed in the IO-IO doublet cohort than the IO-VGF combination cohort.

Then we carried out a subgroup analysis for patients with baseline lymphopenia who did or did not experience recovery from lymphopenia at three months after systemic therapy initiation. Of the 125 eligible patients, 52 patients, accounting for 42%, experienced the recovery from lymphopenia. They had significantly longer overall survival than those who did not, with a medium value of not reached versus 30 months, as shown in this figure. For the next steps, we believe that lymphopenia will become increasingly important prognostic and potentially predictive biomarker for patients with metastatic renal cell carcinoma, particularly in the Europe combination immunotherapy.

Nevertheless, external validation using independent cohorts of patients is required to confirm findings. In addition, we will plan a future molecular study to examine the relationship between the global lymphocytes, that is peripheral blood lymphocytes is assessed in this study, and local lymphocytes that is tumor infiltrating lymphocytes to be assessed on tissue specimens from patients to better understand the underlying mechanisms of lymphopenia in patients with metastatic renal cell carcinoma. Last but not least, we would like to express our sincere appreciation to our patients and their family members who have made this study possible. Many thanks for watching this video and please feel free to read the full article of this study available on Open Access online.