Thursday, June 4, 2015

ASCO 2015: Eosinophilia with Nivo and Pembro - A predictor of success?!!

Changes in blood eosinophilia during anti-PD1 threapy as a predictor of long term disease control in metastatic melanoma.  J Clin Oncol 33, 2015.  Gaba, Victoria, Pineda, et al.

The anti-PD1 antibody Nivolumab and Pebrolizumab have demonstrated improvement in overall survival of melanoma patients.  To date, no lab test has been identified to predict clinical benefit to anti-PD1.  This retrospective observational study looked at patients who received anti-PD1 treatment in a single institution.  The objective was to see if an increase of at least 100/mm3 at 3 wks over the baseline or an increase more than 400/mm3 at 12 wks in the absolute eosinophil counts could predict a clinical benefit.  Results:  From March 2013 - December 2014, 29 patients were treated with anti-PD1 (3 with Nivo, 26 with Pembro).  10.3% were stage M1a, 24.1% were M1b, and 65.5% were stage M1c.  51.7% had elevated LDH.  Patients who experienced an increase in absolute eosinophil counts over the baseline more than 100/mm3 at 3 wks had better response rates (55% vs 9%), progression free survival (9.9 vs 2.6 months), and overall survival (18.8 vs 6.9 months) than those who did not.  Moreover, patients with an absolute eosinophil count more than 400/mm3 at 12 wks responded to treatment (100% vs 18.2%) and showed more benefit regarding progression free survival (18.6 vs 3.6 months), and overall survival (not reached vs 11.4 months) compared to those who did not.  Conclusion:  An increase in AEC of 11/mm3 over baseline at week 3 and an AEC greater than 400/mm3 at week 12 during anti-PD1 treatment might identify patient with melanoma most likely to experience long term disease control with anti-PD1.

A little background:   Eosinophils are white blood cells and one of the immune system components that helps fight off parasites and other infections.  They are also associated with asthma and allergy.  They usually make up 1-6% of a person's total white blood cells.  They are found in tissue around the thymus, the lower GI tract, ovary, uterus, spleen and lymph nodes but NOT in the lung, skin or esophagus.  They can live 8-12 hours in circulation but as long as 8-12 days in tissue.  They develop in the bone marrow and differentiate from other cells in response to cytokines (IL-3, IL-5, and GMCSF.....sound familiar???).  They affect the production of proteins, lipid mediators, enzymes, growth factors and cytokines...all of which play a role in fighting viral infections, mediate allergic response and asthma flares, fight parasites, play a role in mammary gland development, graft rejection, and neoplasia.  Recently it has been discovered that they play a role in antigen presentation to T cells.  Increased levels of eosinophils - eosinophilia - greater than 500 eosinophils/microlitre of blood - is seen in people with intestinal parasites, rheumatoid arthritis, Hodgkins disease, skin disorders, Addisons Disease, esophagitis, and in response to certain drugs like penicillins. The most common cause of eosinophilia is an allergic condition like asthma.

The graph above is from online access to my labs at Moffitt and plot the eosinophil counts from my start in December of 2010.  It is a little hard to match up with the time data points from the article...but it is clear that by Feb of 2011, 12 weeks after my start on Nivo, I had an increase in my absolute eosinophil count from about 140 to 500.  In March of 2011 my eosinophil count per the lab print out was 460.  Clearly, I have spent the past 5 years over my baseline.  Interestingly, B mentioned this phenom at my last visit.  I hadn't noticed this trend!!!  Additionally, Weber had previously told us, at various points, that his patients on anti-PD1 had been found to have eosinophils in their biopsies in everything from skin papules to lung nodules that had looked worryingly like tumor growth.  None were filled with melanoma...just eosinophils.  So.....what does all this mean????  Don't really know.  When you figure in my asthma it just gets more confusing....but there you go!!! - c

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