Immunotherapy for Cancer Attacks Organs

Immune System, Unleashed by Cancer Therapies, Can Attack Organs DEC. 3, 2016

Such drastic and even fatal side effects (unexpected, though not entirely unforeseen) are a significant danger posed by all new medications using new methods that aren’t just variations on the old ones.

Though we cannot know the long-term effects for years or even generations to come, their immense profitability will trump most other concerns. (Remember Thalidomide?)

in the current fervor of anti-opioid sentiment, I fear the same is likely to happen with pain medications. (See previous post: Scientists discover a new class of pain relievers.)

If the search to discover a new non-opioid/non-addictive pain medication ever succeeds, all pain patients would be forced to use the new drug – for our own safety, of course.

In the rush to get a blockbuster like this to market, greed will rule above all else, development will be rushed, trial statistics will be manipulated, side effects will be hidden, government approvals will be virtually guaranteed, and the investors will make a killing while pain patients are forced to be their long-term test subjects.

As Chuck Peal [61 yrs old] lay in a Waterbury, Conn., emergency room, … he appeared to be dying, and they were not sure why.

A doctor suspected a heart attack, but uncertainty left him urgently researching the situation on his phone.

This was not a heart attack. Mr. Peal’s body was attacking itself, a severe reaction by his immune system that was a side effect of a seemingly miraculous cancer treatment aimed at saving his life.  

In the seven weeks prior, doctors at Yale had combated Mr. Peal’s melanoma with two of the most promising drugs in cancer treatment today.

These medicines work by stimulating the immune system to attack cancer as ferociously as it does other threats, like viruses and bacteria.

These so-called immunotherapy drugs have been hailed as a breakthrough in cancer treatment, attracting billions of research dollars and offering new hope to patients out of options.

But as their use grows, doctors are finding that they pose serious risks that stem from the very thing that makes them effective.

An unleashed immune system can attack healthy, vital organs: notably the bowel, the liver and the lungs, but also the kidneys, the adrenal and pituitary glands, the pancreas and, in rare cases, the heart.

Doctors at Yale believe immunotherapy is causing a new type of acute-onset diabetes, with at least 17 cases there so far, Mr. Peal’s among them.

In cancer clinics around the world, and in drug trials, myriad other side effects are showing up. Studies are finding that severe reactions occur nearly 20 percent of the time with certain drugs, and in more than half of patients when some drugs are used in combination.

Another recent paper found that 30 percent of patients experienced “interesting, rare or unexpected side effects,” with a quarter of the reactions described as severe, life-threatening or requiring hospitalization.

Some patients have died, including five in recent months in clinical trials of a new immunotherapy drug being tested by Juno Therapeutics Inc

The upshot, oncologists and immunologists say, is that the medical field must be more vigilant as these drugs soar in popularity. And they say more research is needed into who is likely to have reactions and how to treat them.

“We are playing with fire,” said Dr. John Timmerman, an oncologist and immunotherapy researcher at the University of California, Los Angeles, who recently lost a patient to side effects

We’ve heard about immunotherapy as God’s gift, the chosen elixir, the cure for cancer,” he said. “We haven’t heard much about the collateral damage.”

In the meantime, these drugs are moving from academic centers into cancer clinics across the country, where oncologists in smaller cities most likely have less experience with the side effects

And with lives to be saved and billions of dollars to be made$250,000 or more is the list price for a year of some regimens — not enough research has been done into the risks of the new therapies

It is “a massively understudied area,” Dr. Murphy said, adding: “The No. 1 priority is anti-tumor effects. Everything else, however severe, is considered the price worth paying.

Other research, however, shows that the promise comes with real risks.

A 2015 paper in The New England Journal of Medicine showed that use of these drugs carried a risk of side effects that were severe, required hospitalization or were life-threatening 54 percent of the time.

One study co-authored by Dr. Kluger found positive responses in more than 40 percent of advanced melanoma patients when they used a combination of two major immunotherapy drugs, nivolumab and ipilimumab

The effectiveness of immunotherapy drugs and their side effects are intimately bound by the same biological mechanisms.

Called checkpoint inhibitors, the drugs work by essentially reversing a trick that cancer plays on the immune system: The cancer cells send nefarious signals to immune-system cells that cause them to stand down. Cancer is turning on the immune system’s brake.

There is a valuable reason the brake exists: It can shut down the body’s powerful defenders so that they do not inadvertently attack the body itself. Cancer is taking advantage of this key survival mechanism.

Cancer cells can avoid destruction by taking advantage of a switch on the T-cell called an immune checkpoint. The checkpoint can shut down the T-cell and suppress the immune response, allowing the cancer to grow undisturbed.

When an immunotherapy drug turns the brake off, the immune system can sometimes shrink tumors in mere days.

However…

“Old or fat mice were literally dead within hours,” said Dr. Murphy, the professor at Davis who believes too little is being done. He is well positioned to see the trends: In the past year, he sat on eight government grant review committees focused on immunotherapy, and he said only three out of 500 research proposals he reviewed focused on the toxicity side of immunotherapy.

Thus far, only a modicum of work has been done on these questions. Several studies found that older mice were more susceptible than younger mice to autoimmune reactions; another study, also in mice, found that obese subjects were more likely to have adverse effects.

Then came the TeGenero tragedy in 2006.

TeGenero Immuno Therapeutics designed a drug to stimulate the immune system to fight leukemia. At Northwick Park Hospital in London, a Phase 1 trial took place, with six healthy patients getting the drug. Within hours, all suffered multiorgan failure.

The devastating results tempered the enthusiasm and suggested that more work needed to be done in advance of human trials. But enthusiasm came roaring back.

Part of the reason was that, ultimately, the autoimmune reactions were seen not only as an acceptable cost of these drugs but as evidence they were working.

“It’s the nature of the beast,” said Martin Bachmann, a professor and immunologist at the Jenner Institute, which is affiliated with Oxford University.

I wonder which “beast” he’s referring to, the money that’s corrupting science or the body-wide effects of such immunotherapies.

“I’m not sure you can get rid of the side effects — it’s really what you want.”

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  1. Pingback: Inhibition of Nociceptors: Interpret Results With Caution | EDS and Chronic Pain News & Info

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