Pembrolizumab Controls Mesothelioma in 76 Percent of Test Patients

The immunotherapy drug pembrolizumab shriveled pleural mesothelioma tumors, or at least caused them to stop growing, in fully three-quarters of the mesothelioma patients treated with it.

So say researchers from the Perelman School of Medicine at the University of Pennsylvania who presented this observation at the annual meeting of the American Association for Cancer Research in Philadelphia.

Pembrolizumab is a drug the U.S. Food and Drug Administration (FDA) approved last year for treating melanoma.

The University of Pennsylvania findings may someday soon help convince the FDA to also approve pembrolizumab for the treatment of pleural mesothelioma, the researchers indicated.

Pembrolizumab is a humanized monoclonal antibody that targets programmed cell death protein 1 — known as PD-1, in science shorthand.

Pembrolizumab works by preventing PD-1 from interacting with two of its ligands that are present in mesothelioma cells. Those ligands are labeled PD-L1 and PD-L2.

By preventing this interaction between PD-1 and the ligands, pembrolizumab disrupts mesothelioma’s ability to suppress the body’s natural immune-system reaction to the presence of cancer cells.

When cancer cells show up, the immune system’s T-cells are supposed to be activated. T-cells are a type of lymphocyte designed to execute frontal, flanking, and pincer-style assaults on invading microorganisms.

But mesothelioma cells possess the ability to keep T-cells penned up in their harbors.

Pembrolizumab changes the equation so that the T-cells are able to weigh anchor, shove off and aggressively do battle with those mesothelioma cells.

More than Two Dozen Mesothelioma Patients Participate in Study

The researcher’s findings are not yet complete, but already they feel confident that — in pembrolizumab — they may have a winner against malignant pleural mesothelioma.

“The disease control rates observed in this study are very encouraging,” said Penn Mesothelioma and Pleural Program co-director Evan W. Alley, M.D., Ph.D.

Alley is the lead researcher in this investigation. Joining him have been scientists from mesothelioma centers elsewhere in the U.S., as well as from Europe.

To conduct their study, the research team enrolled a cohort of 25 mesothelioma patients and gave pembrolizumab to each.

In more than one-quarter of the patients, mesothelioma tumors receded. In nearly half of the patients the mesothelioma tumors stopped growing.

Those numbers translated into a 76 percent rate of disease control — a very promising result indeed, the researchers indicated.

Importantly, pembrolizumab appeared to be tolerated by the group; none of the patients suffered serious side effects.

That’s not to say there were no side effects at all. But those that did crop up were readily manageable, the researchers said.

Penn Medicine Is Major Mesothelioma Research Center

One reason for the excitement over pembrolizumab is that it could become the first FDA-approved therapy for use on malignant pleural mesothelioma patients whose disease has progressed despite receiving standard therapy.

Wide availability of pembrolizumab could prove a boon to mesothelioma patients, since response rates to current treatment options after standard therapy are in the range of less than 10 percent, the researchers say.

Penn Medicine’s breakthrough with pembrolizumab is unsurprising to mesothelioma patients familiar with the academic medical center. It’s among the world’s finest in terms of biomedical research.

Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania and the University of Pennsylvania Health System.