Refining intermediate-risk (IR) stratification in patients (Pts) with metastatic renal cell carcinoma (mRCC) receiving first-line (1L) immunotherapy (IO) within one year of diagnosis (Dx): Findings from the International Metastatic Renal Cell Carcino

4556 Background: The IMDC risk model is pivotal for predicting clinical outcomes in pts with mRCC, yet variability exists within the IR group. Moreover, therapy initiation within < 1 year post dx, a predominant IMDC risk factor, significantly influences prognosis. Thus, this study evaluates this heterogeneity in IO era, focusing on patients receiving 1L IO within < 1 year post dx. Methods: Data from pts with mRCC receiving 1L IO within < 1 year post dx, with IMDC score of 1 or 2, were retrospectively collected from the IMDC. Score 1 pts were defined as those who started treatment < 1 year post dx, while score 2 pts had an additional IMDC risk factor: low hemoglobin (Hb), Karnofsky Performance Status (KPS) < 80, high neutrophil, high calcium (Ca), or high platelet (Plt) count. We assessed overall survival (OS) and time to treatment failure (TTF) using Cox regression, adjusting for age, sex, nephrectomy status, histological type, presence of one or more metastases, and 1L regimen type (IO+IO vs. IO+VEGF). The response was evaluated according to RECIST 1.1 criteria. Results: Of the 670 pts initiating 1L IO < 1 year post dx, 331 had an IMDC score of 1, and 339 had a score of 2, subdivided into 5 subgroups as detailed in the table. Pts' median age was 62 years (IQR: 55-69). Median follow-up was 16.6 months. Response rates, 18-month OS, and 6-month TTF rates for each group are shown in the table. Adding the factor of treatment initiation < 1 year post dx, the high neutrophil count has the most significant effect on OS (HR = 4.85, 95% CI: 2.61-9.03, p < 0.001). Also, KPS < 80 significantly affects both OS (HR = 3.93,95%CI = 2.26-6.84), p < 0.001) and TTF (HR = 1.59 95%CI = 1.02-2.61, p = 0.04). Low hemoglobin, as well as high calcium, notably worsen OS without significant impact on TTF. High Plt count shows no significant impact on OS and TTF, possibly due to the low prevalence of this risk factor (15/670). Conclusions: Additional risk factors can affect the prognosis of pts with mRCC receiving IO < 1 year post dx. Integrating other biomarkers or radiological features could refine risk stratification, enhancing treatment approaches for IR pts. % response 18-month OS rate Adj. HR for OS (95% CI) 6-month TTF rate Adj. HR for TTF (95% CI) IMDC=1 Ddx to start ttt<1 year (N=331) 46% 85% REF 65% REF IMDC=2 Dx to start ttt<1 year+ Low Hb(N=255) 37% 73% 1.83(1.33-2.5) p=0.002* 56% 1.04 (1.02-2.48) P=0.66 Dx to start ttt<1 year+ KPS<80 (N=30) 30% 57% 3.93 (2.26-6.84) p<0.001* 50% 1.59(1.02-2.61)P=0.04* Dx to start ttt<1 year+ High Neutrophils (N=22) 9.1% 51% 4.85(2.61-9.03)p<0.001* 41% 1.41(0.86-2.34)P =0.16 Dx to start ttt<1 year+ High Ca (N=17) 35% 67% 2.68(1.27-5.62)p=0.01* 65% 1.09(0.62-1.93)P=0.75 Dx to start ttt<1 year+ High plt (N=15) 33% 63% 2.08(0.83-5.23)p=0.11 42% 1.29 (0.69-2.38)P=0.42