Melanoma Coverage from Every Angle

Do PPIs Affect the Efficacy of Immunotherapy in Metastatic Melanoma?

By: Melissa E. Fryman, MS
Posted: Wednesday, January 2, 2019

According to an analysis of data from the CheckMate 069 trial, the use of proton pump inhibitors (PPIs) in patients with melanoma seemed to decrease the efficacy of immunotherapy with nivolumab plus ipilimumab. However, no apparent reduction in efficacy was seen in patients who received PPIs and ipilimumab monotherapy. Krisztian Homicsko, MD, PhD, of the Lausanne University Hospital, CHUV, in Lausanne, Switzerland, and colleagues, reported their results at the 2018 European Society for Medical Oncology (ESMO) Immuno-Oncology Congress in Geneva (Abstract LBA2).

In this retrospective analysis of data from 140 patients with previously untreated, unresectable, or metastatic melanoma, the authors assessed the effect of different classes of co-medications on the efficacy of immunotherapy. They found that in patients receiving the combination of ipilimumab and nivolumab for whom PPIs were detected at baseline, the objective response rate was approximately half that of patients who had no detectable PPIs in baseline bloodwork. The efficacy of immunotherapy was also reduced in terms of progression-free and overall survival . Pretreatment serum samples for these patients showed changes in levels of NCAM1 and CSF3R as well as an increase in blood levels of leukocytes and neutrophils.

The negative effect of PPIs in patients with melanoma was confirmed in another cohort of patients receiving nivolumab or pembrolizumab monotherapy. However, the authors noted that the negative effect was not seen in patients receiving ipilimumab monotherapy.

“PPIs might establish a unique inflammatory immune status prior to immune therapy initiation that interferes with treatment efficacy. These results suggest that if possible, PPIs should be avoided in patients [treated with] PD-1–based immun[o]therapies,” concluded the authors.

Disclosure: Study authors’ disclosure information may be found at Annals of Oncology.

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