Ipi Were a Rich Man

Calling my cancer drug "ipi" is a little too cute for my taste but its generic name, ipilumumab, leaves me tongue-tied and the trade name Yervoy is just plain dumb; it sounds like a character from "Fiddler on the Roof." So henceforth in The Ogler, ipi it will be.

Regardless of what it’s called, enormous hopes have been hitched to this new immunotherapy agent. That’s no surprise, given the dearth of treatments that can arrest the advancement of stage IV melanoma. The problem with the drug is that it’s usually unsuccessful, it costs a fortune and it comes with side effects, some of them potentially fatal.

That really makes you want to play music on a rooftop, doesn’t it?

I’ve been digging around for days to find the best definition of ipi’s mechanism of action. I want to understand how it works. Doctors and nurses who should know this either don’t or are disinclined to use adult language in describing it. Their lame metaphors usually involve military weapons or car parts. That’s left me to patch together on my own the following definition drawn from what I’ve read online and in books about immunology:

For the visually inclined, perhaps
this schematic will help

Cancer cells produce antigens, which are proteins on the exterior of the cell that stimulate the immune system to produce antibodies against them. These antigens are recognized by dendritic cells, which present the antigens to cytotoxic T lymphocytes. These "killer T cells" then recognize these cells as cancer on the basis of these antigens and destroy them.

There is a catch, however. In presenting the antigens to T cells, these dendritic cells also present an inhibitory signal dubbed CTLA-4 that binds to receptors on the T cells and turns off the cytotoxic reaction. This allows the cancer cells to survive. A manmade monoclonal antibody, ipi comes to the rescue by blocking this CTLA-4 inhibitory signal, and allows the T cells to destroy the cancer cells (melanoma cells, at least).

As simplistic as this definition would be to an immunologist, it leaves even me confused—and I’m the one who wrote it. What I still want to know is: How does ipi create this blockade of the CTLA-4 receptor? What does it do? And when that soluble formulation of ipi is pumped into my vein in the infusion lab, what’s actually in it? For a drug treatment billed at $30,000 per infusion, shouldn’t someone know and be able to explain—to the patient perhaps?—what the hell it’s doing inside the body and how?

What is known about ipi is that it’s the first drug shown to prolong the lives of people with late-stage melanoma. There are about 9000 of us in the U.S. right now. A randomized, controlled clinical trial, reported in the New England Journal of Medicine, showed that ipi could extend patient survival. In the trial, patients with advanced melanoma were randomly assigned to receive either ipi or an experimental melanoma vaccine. Those who received ipi lived a median of 10 months after enrolling in the trial compared with a median of 6.5 months for those who received the vaccine.

People like me are eager to grab hold of the fact that while the drug added less than four months of life on average, about 20% of patients in the trial had an impressively durable response to the drug. Some are still alive today, at least nine years after starting their treatment.

“There are some people who we have treated with ipilimumab whose scans look just as abnormal now as they did five years ago, so it has turned it (melanoma) into a chronic disease,” said Dr. Jedd Wolchok, director of immunotherapy at Memorial Sloan-Kettering Cancer Center in New York. “It changed the situation from something they were dying from into something they are living with. That really does show you that the immune system can restore an equilibrium between the person and the tumor.”

My case is complicated by the type of brain tumor I had, which is why my follow-up treatment involves more than just ipi. There was a small study published earlier this year that suggests a synergy between ipi and whole-brain radiation, which provides me with another glimmer of hope. I won’t attempt to describe this interaction in scientific terms, other than to say that melanoma cells blown to bits by radiation provide extra morsels for ipi to feast upon and thereby boost the immune system. There now, that's a definition that should make perfect sense to everyone.