Early clinical markers of response to first-line treatment with immune checkpoint inhibitors (ICI) and VEGF inhibitors (VEGFI) in metastatic renal cell carcinoma (mRCC) are lacking. We explore whether baseline and dynamic changes in haemoglobin (Hb) is associated with treatment response and disease progression.
We performed a retrospective analysis of 185 mRCC patients treated between January 2014 and July 2021 across 2 tertiary cancer centres in the UK and the Netherlands. 100 patients received first-line treatment with ICI alone, 56 with VEGFI alone and 29 with combination ICI/VEGFI. Hb at baseline, 6 and 12 weeks after commencing treatment, and at disease progression were collected. First radiological disease assessment occurred at 12 weeks. Patients who received Hb transfusions were excluded.
Responders to ICI experienced a significant increase in Hb at week 12 (n = 66, mean ± SE: 7.12 ± 2.28, p = 0.01), a trend which was not seen in non-responders (n = 33, mean ± SE: -0.34 ± 1.84, p = 0.49). Responders had a higher baseline Hb than non-responders (mean ± SE: 7.69 ± 5.53, p = 0.1), and this intergroup difference increased at week 6 and 12 (mean ± SE: 14.8 ± 5.08, p = 0.01). Non-responders to VEGFI showed a significant reduction in Hb at week 12 (n = 39, mean ± SE: -7.13 ± 2.3, p = 0.01). This trend was not significant in responders (n = 17, mean ± SE: -6.24 ± 2.77, p = 0.1). Responders had a significantly higher Hb at all three timepoints. Amongst patients on ICIs with progressive disease, a decrease in Hb from baseline was associated with a shorter progression-free survival (PFS) when compared with an increase in Hb (median: 2.6 vs 4.7 months, p = 0.01). This was not observed in patients receiving VEGFI (p = 0.7) or ICI/VEGFI (p = 0.3).
An increase in Hb at 12 weeks of receiving treatment predicts response to first-line ICI. In contrast, a significant decrease in Hb is associated with resistance to VEGFI treatment. Higher baseline Hb levels are associated with response to both ICI and VEGFI treatment. Increasing Hb in patients receiving ICIs may be positively prognostic for longer PFS. This study suggests that baseline and dynamic changes in Hb levels are early markers of outcome in the first-line treatment of mRCC.
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All authors have declared no conflicts of interest.