Low versus low-intermediate risk metastatic renal cell carcinoma (mRCC): Contemporary data from the International mRCC Database Consortium (IMDC).
Authors: El Hajj Chehade Razane , Xie Wanling , Semaan Karl , Eid Marc , Machaalani Marc , Nawfal Rashad , Saad Eddy , Saliby Renee Maria , Steiner Clara , Yekeduz Emre , Wells Connor , Maj David , Zarba Martin , Pal Sumanta Kumar , Suárez Cristina , Takemura Kosuke , Basappa Naveen S. , Baca Sylvan C. , Heng Daniel Yick Chin , Choueiri Toni K. 
Published: February 2025

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Background:
The IMDC model has been effectively used to predict patients’ (pts) outcomes with mRCC, significantly guiding treatment decisions in the era of immune checkpoint inhibitors (ICIs) that have improved survival. In this study, we aim to characterize the clinical outcomes between patients classified as low (L, IMDC score of 0) vs. low-intermediate (L/I, IMDC score of 1) categories.
Methods:
Data of pts with mRCC receiving first-line (1L) ICI-based therapies with IMDC scores 0 or 1 was collected from the IMDC. Pts with score 1 were further subdivided into 4 groups based on their individual risk factor: low hemoglobin (Hb), Karnofsky Performance Status (KPS) <80, time from diagnosis (dx) to treatment < 1 year, and other risk factors including elevated neutrophils, platelets, and calcium. Overall survival (OS) and time to treatment failure (TTF) were analyzed using Cox regression models. Logistic regression was used to compare an objective response rate (ORR) according to RECIST 1.1.
Results:
Among the 803 eligible patients, 283 were classified as L and 520 as L/I. Patients' median age was 60 years (Q1-Q3: 23-88 years). The distribution of patients across specific risk categories within the IMDC score 1 group is detailed in the table. Compared to those with an IMDC score of 0, patients with a score of 1 related specifically to low performance status was associated with a shorter TTF (HR: 2.93, p<0.0001) and ORR (OR: 0.24, p=0.002). Anemia was significantly associated with decreased OS (HR: 1.61, p=0.002), shorter TTF (HR: 1.63, p=0.0002), and reduced ORR (OR: 0.65, p=0.05). Time from diagnosis to initiation of treatment within 1 year was significantly associated with shorter TTF (HR: 1.39, p=0.0015).
Conclusions:
Anemia and low-performance status emerged as the most informative factors differentiating prognosis between L and L/I IMDC risk groups receiving 1L ICI-based treatment. Molecular studies could further clarify these differences, aiding risk stratification and personalized treatment.

Clinical outcomes of patients with mRCC based on risk factors.

IMDC =0(N=283)
IMDC=1

Low Hb(N=133)

Time from dx to treatment <1 year (N=331)

KPS <80
(N=21)

Other risk factors (N=35)

HR for OS* (95% CI)
Ref.
1.61 (1.08-2.42)p-value = 0.002
1.11 (0.8-1.56)p-value = 0.55
1.9(0.819-4.408)p-value = 0.135
1.16 (0.55-2.42)p-value = 0.7

HR for TTF* (95% CI)
Ref.
1.63 (1.26-2.10)p-value = 0.0002
1.39(1.13-1.7)p-value = 0.0015
2.88 (1.73-4.774)p-value <0.0001
1.9 (0.73-1.91)p-value = 0.47

OR for ORR** (95% CI)
Ref.
0.65 (0.42-0.99)p-value = 0.05
1.1 (0.8-1.52)p-value = 0.52
0.22 (0.05-0.66)p-value = 0.02
0.99 (0.48 – 2)p-value = 0.98

*Analysis included 781 patients for OS and 778 for TTF after excluding cases with missing data.

**78 not evaluable patients were included as non-responders.