Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab
Menée à partir de données portant sur 720 patients atteints d'un mélanome de stade avancé traité par ipilimumab (durée médiane de suivi : 16,5 mois), cette étude évalue l'association entre le niveau de neutrophiles avant traitement, un indicateur dérivé du rapport neutrophiles/lymphocytes et la survie des patients
Background : Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need.
Patients and methods : Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access programme were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cut-off for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR, and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also performed.
Results : The median follow-up was 16.5 months. The optimal cut-off for dNLR was 3. Baseline ANC and dNLR were significantly associated with outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P<0.0001 for all). Further, for each elevated variable, prognosis worsened. Patients with both ANC≥7500 and dNLR≥3 had a significantly and independently increased risk of death (HR=5.76; 95%CI: 4.29-7.75) and of progression (HR=4.10; 95%CI: 3.08-5.46) compared to patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1-year and 2-years survival rates were 2% and 0%, respectively, for patients with ANC≥7500 and dNLR≥3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR.
Conclusions : Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease management strategies. Further, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials.
Annals of Oncology , résumé, 2016