Powerful New Cancer Treatments Come With Rare Risks for Some

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10 September 2017

A potent new generation of therapies that harness the body’s immune system has brought promising results for deadly cancers, and also some unpredictable side effects -- ranging from a light rash to shingles to severely damaged organs. When or if they’ll strike is anyone’s guess, according to Bloomberg.

“It’s such a roll of the dice,” said Betsy Plimack, an oncologist with expertise in bladder cancer at Fox Chase Cancer Center in Philadelphia. “It’s high risk, high reward. Maybe you’ll be one of those people who have zero side effects and whose tumor shrinks, or maybe your tumor will grow right through it and you’ll be debilitated with some autoimmune event.”

For many patients, the risk is worth it. The drugs, known as immunotherapies, have prolonged lives and sometimes put what seemed like incurable tumors in remission, even after other treatments failed.

‘Almost Dying’

Tom Reilly knows first-hand: one of the life-saving treatments almost killed him. The 63-year-old investment management executive from Hingham, Massachusetts, was diagnosed in 2009 with advanced melanoma, the most deadly form of skin cancer. He enrolled in a clinical trial for what would become the first immunotherapy approved in the U.S., Bristol-Myers Squibb Co.’s Yervoy.

For 11 months, Reilly had no side effects. Disappointed, he thought he was getting the placebo. Reilly was heading to an out-of-town golf tournament in October 2010 when the stomach cramps and diarrhea started. That night, he started to bleed heavily from his rectum.

“You’re on the drug! You feel like you scratched a lottery ticket and won, but you’re almost dying,” Reilly said in a phone interview.

Stories like Reilly’s have played out across the country since 2011, when Yervoy came to the market. The drug was followed by the arrival of blockbuster treatments including Merck & Co.’s Keytruda, a drug for cancers including melanoma and lung cancer that analysts predict will reach more than $11 billion in sales in 2023.

As drugmakers seek approval for more cancers and combine treatments to increase their potency, more complications will arise. The safety risks could ultimately limit the drugs’ use.

This week, U.S. regulators suspended several experimental trials using cocktails of immunotherapy drugs in patients with multiple myeloma and other blood cancers. Clinical studies being run by Bristol-Myers, Celgene Corp., AstraZeneca Plc and Roche Holding AG were paused after patients with multiple myeloma died in a trial of Merck’s Keytruda.

“There’s no obvious cause that’s standing out,” Roy Baynes, Merck’s global clinical development chief, said in an interview Saturday. “These are oftentimes very old patients. They’re oftentimes quite ill. And it’s possible that you’re just looking at, essentially, cumulative toxicity of treatments.”

The new side effects can be overlooked even by professionals. When Reilly called his doctor’s office with food-poisoning-like symptoms, he was told to take the common diarrhea drug Imodium while he waited to be seen. Only later was he diagnosed with ulcerative colitis, a far more serious condition.

“The whole field of medicine needs to learn more about these side effects,” said Lecia V. Sequist, associate professor of medicine at Massachusetts General Hospital.

Toxicities Emerge

The latest research on the topic will be presented at the European Society for Medical Oncology meeting underway in Madrid, one of of the largest gatherings of researchers, drugmakers and oncologists. It includes sessions on when to discontinue immunotherapy, information on how to manage side effects and insights on predicting which toxicities will emerge.

For patients on therapies that use the immune system, there are subtle changes that might require an urgent visit, said Jennifer Litton, chief of clinical research in the breast medical oncology department at M.D. Anderson Center in Houston. She pointed to diarrhea, shortness of breath or a rare headache -- symptoms that wouldn’t necessarily be worrisome in patients using other types of drugs.

In many cases, though, patients feel fine. About 40 percent of people treated for gastrointestinal cancer with the novel medicines don’t have a single side effect, according to Plimack of Fox Chase Cancer Center in Philadelphia.

“With immunotherapy, you have to treat a lot of people before you see these really rare ones,” said Bruce Johnson, president of the American Society of Clinical Oncology.

Weakened Immune System

Patients don’t always tell their doctors when realize something is wrong. Some fear they will be taken off the drug or given a lower dose. Others think it’s just a sign the treatment is working.

And some, like Reilly, don’t realize the severity of their condition. When the stomach cramps started, he called his oncologist, but finished his golf tournament in Westchester, New York, anyway. When he got back home, he was admitted to Massachusetts General Hospital, the start of a months-long ordeal trying to heal his intestinal tract.

A host of other side effects then flared up, including thrush and shingles in the eyes -- every virus that came along because of his weakened immune system.

“Your body becomes a sponge for any infection that’s out there,” Reilly said.