NLR may be a prognostic marker for mRCC treated with immune checkpoint blockers

A new study has shown that high 6-week neutrophil-lymphocyte ratio (NLR) is associated with poorer outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint blockers (ICBs). The findings were published in the Journal for Immunotherapy of Cancer.

The study, led by Aly-Khan A. Lalani, MD, at the Dana-Farber Cancer Institute in Boston, MA, investigated the association of baseline NLR and changes during treatment with outcomes in mRCC patients treated with conventional ICBs.

Recently, second-line treatment for mRCC has expanded to include ICBs, such as nivolumab, a programmed cell death protein-1 (PD-1) antibody. In addition, other PD-1 and its ligand (PD-L1)–based therapies are under investigation to treat RCC.

Prior research has shown that an elevated NLR at baseline was associated with poor prognosis in some solid tumors, but it has not been well-defined for mRCC.

This retrospect analysis included all patients treated with PD-1/PD-L1–based treatment regimens at the Dana-Farber Cancer Institute (DFCI) from 2009 to 2017. The NLR was measured at baseline and at 6 (±2) weeks to evaluate the prognostic value of change in NLR on outcomes.

A total of 142 patients were identified; the median age was 61 years. Most patients (84.5%) had clear cell histology, more than half (60%) were intermediate risk, 18.3% had favorable risk, and 21.8% were poor risk based on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors.

Overall, 91 patients received PD-1–based therapy (71 monotherapy, 20 combination therapy) and 51 received PD-L1–based therapy (5 monotherapy, 46 combination therapy). Forty-six patients received standard of care PD-1 monotherapy and 96 were treated as part of a clinical trial.

The median NLR was 3.9 (range: 1.3-42.4) at baseline and 4.1 (range: 1.1-96.4) at 6 (±2) weeks.

Median follow-up since initiation of the anti-PD-1/PD-L1 treatment was 16.6 months. Median duration on therapy was 5.1 months.

The observed objective response rate (ORR) was 31%, and median progression-free survival (PFS) and overall survival (OS) after therapy initiation were 7.3 months and 29.6 months, respectively.

Baseline NLR levels were significantly higher in the poor IMDC risk group compared to those with favorable or intermediate risk (P <0.001). A higher baseline NLR showed a trend toward lower ORR, shorter PFS, and shorter OS.

In general, the NLR at 6 weeks was a stronger predictor of all three outcomes than baseline NLR. A higher 6-week NLR was independently associated with a lower ORR, shorter PFS, and shorter OS. A decrease ≥25% (regardless of baseline levels) was associated with an improved PFS and significantly better OS when compared to the no-change reference group.

The investigators point out that the retrospective design has the potential for selection bias and confounders. In addition, they were not able to control for use of concomitant medications that could have influenced white blood cell counts. Furthermore, at the time of the study PD-L1 expression was not known, and data from untreated patients were not available.

“In our cohort of mRCC patients treated with PD-1/PD-L1–based immune checkpoint blockade, higher 6-week NLR was independently associated with a worse ORR and shorter PFS and OS,” the authors wrote.

Prospective studies to validate the results are needed.

To read more about this study, click here.