Saturday, June 6, 2015

Lab values that may predict response to Ipi/Yervoy????

This article is not from ASCO, but I thought it was interesting after my last post on eosinophilia being associated with a response to anti-PD1...

Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients.  Br J Cancer, 2015, May 26.  Ferrucci, Gandini, Battaglia, et al.

Ipi improves survival of metastatic melanoma patients.  Despite documented, durable objective responses, a significant number of patients fail to benefit.  Patients treated at 3 Italian institutions - 187 dosed with 3 mg/kg ipi and 27 with 10mg/kg ipi - were evaluated.  Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy blood counts.  In the training cohort of 69 patients, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses.  Patients with baseline NLR less than 5, had a significantly improved progression free survival and overall survival compared to those with a NLR equal or greater than 5.  Associations of low NLR with improved survival were confirmed in three validation cohorts.

Background info:

Neutrophils are the most frequent kind of white blood cell (40-75%) we have.  They form from stem cells in the bone marrow.  They live only 5-90 hours.  They can undergo chemotaxis, which allows them to travel rapidly to the site of an infection or inflammation.  Once there, they release cytokines that increase the inflammatory process and attracts other cells to the area.  They can ingest microorganisms or particles, thereby helping fight off disease.  Low neutrophils = neutropenia, can happen in anemia, in some types of leukemia, or be caused by medicines like chemo....leaving the person at risk for infection.

Lymphocytes are any of 3 types of white blood cell:  natural killer cells, T cells or B cells, all of which play a role in immunity.  They are the main cell found in lymph, ergo the name.  They live for weeks to years to a lifetime (a good thing when thinking about immunity!!), much longer than other white cells.  NK cells generally kill viruses and tumor cells.  Helper T cells release cytokines and growth factors that regulate other immune cells.  Cytotoxic T cells also kill cells infected with viruses and tumor cells.  B cells work in the secretion of antibodies.  Increased levels of lymphocytes - lymphocytosis - is often a sign of a viral infection.  Increased lymphs in the presence of decreased numbers of neutrophils can be due to lymphoma. Decreased lymphocytes - lymphocytopenia - is usually due to infection (like HIV), surgery or trauma and leaves the person immunocompromised.

A simple test from a basic blood collection is a CBC, which is a complete blood count. It tells you the number of red blood cells, white blood cells, hemoglobin, hematocrit, sizes of various cells, and the number of platelets in your blood.  A differential is usually run with the CBC and it breaks down the number of all the white blood cells.  Normal counts of the various white blood cells are broken down in percentages: 
  • Neutrophils: 40% to 60%
  • Lymphocytes: 20% to 40%
  • Monocytes: 2% to 8%
  • Eosinophils: 1% to 4%
  • Basophils: 0.5% to 1%
  • Bands (young neutrophils): 0% to 3%
All this to say.... IF this report holds true, it would be pretty easy to test a person for their number of lymphocytes and neutrophils, compute the ratio, and determine whether they are likely to benefit from treatment with ipi.  If the answer is no....we could avoid wasting time, treasure, avoid an ineffective treatment with the potential for side effects, and move them forward to a treatment that WILL provide benefit!!! I guess time will tell! - c


  1. It has been almost 3 years since my IPI treatment. Though I do not qualify for PFS I believe, I can report that I have had only 2 metastases show up since. I checked my NLR pre-therapy and it was exactly 3. Perhaps it was a good indicator in my case. The 1 metastasis that I still have and is inoperable seems to have ceased growing. Another good sign that the ipi treatment may still be having an effect along with the freedom from others.

  2. That is wonderful, Frank!! (Well, not when you were dealing with the mets....I remember that mess....but that you have in fact eradicated the two and the other seems rendered inactive!!) Time will tell about all these lab markers and tumor testing as it will for the NLR. However, it seems to be ringing true for many...including you...and is something we certainly have drawn all the time! Very happy for you. Hang in there.