Wednesday, February 3, 2016

Neutrophils as a prognostic predictor in patients treated with ipi/Yervoy



Back in June, I posted this:  Lab values that may predict response to ipi/Yervoy   The article discussed baseline neutrophil-to-lymphocyte ratios specifically.  Here is an expanded study by the same lead author.

Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab.  Ferrucci, Ascierto, Pigozzo, et al.  Ann Oncol. 2016 Jan 22.

"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.
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.
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. Further, for each elevated variable, prognosis worsened. Patients with both ANC≥7500 and dNLR≥3 had a significantly and independently increased risk of death  and of progression 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."

So....elevated absolute neutrophil counts as well as elevated neutrophil-to-lymphocyte ratios did not bode well for the 720 melanoma patients treated with ipi in this study.  The risk for progression and death was even greater when both of those values were increased.  This report is consistent with the findings from the initial, smaller study of  214 melanoma patients treated with ipi in which:  "Patients with baseline NLR (neutrophil-to-lymphocyte ratio) less than 5, had a significantly improved progression free survival and overall survival compared to those with a NLR equal or greater than 5."

For what it's worth....c 

2 comments:

  1. Interesting. Depending on when you pick your baseline... I just ran all my husband's ANC and ALC data and when he was in crisis, pre-chemo, the dNLR was as high as 15.5. Two months later when he started ipi, it was 2.2. Ipi also happened not to work for him. For what it's worth. :)
    C

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  2. I presume from the way "baseline" is used in this study...it would mean pretreatment (of any sort) levels...but it is not terribly clear and presents even more confusion for those like your husband who undergo sequential treatments. Wishing you both my best.

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