'Game-changer' cancer drug celebrates 20 years. Gleevec turned a death sentence into a chronic disease for many.

In the mid-1990s Mel Mann was counting down his days. His doctor had given him three years to live, and time was running out.

Mann's chronic myeloid leukemia diagnosis had prompted him to retire from the Army and move to Atlanta, where he split his time between his young daughter and running bone marrow drives.

His best chance for longer survival was a bone marrow transplant, but as a Black man without a matched sibling, his chances of finding a donor were slim. The previous year, only 20 African Americans had been able to find matches out of 2,000 who needed them, he remembered.

In 1998, at the three-year mark, his white blood cell count started climbing, suggesting his cancer was about to take a turn for the worse. "I was getting scared," he said.

Then Mann's oncologist called from Houston to say that a clinical trial he'd been waiting for had opened up. Mann would be among the earliest patients to try a new medication called Gleevec. He might get a dose too low to be effective and the drug might not work at all, the doctor warned. But Mann agreed right away.

Nine months later he ran a marathon in Alaska. And then another in Canada.

Based on the success of such clinical trials, Gleevec was approved by the Food and Drug Administration exactly 20 years ago, on May 10, 2001.

The drug initiated a new era in cancer care, where characteristics of the tumor – rather than its original location – determined what treatment a patient would get.

"It revolutionized the way physicians and scientists began to think about how to treat cancer," said Louis DeGennaro, president and CEO of The Leukemia & Lymphoma Society. "It was the birth of precision medicine: the right drug to the right patient at the right time."

Although Gleevec remains one of the most powerful of these targeted therapies, approved for treating 11 kinds of cancer including Mann's type of leukemia, many similar drugs have followed, transforming treatment for lung cancer and other tumor types.

DeGennaro, who was a pharmaceutical executive back then, said the impact of Gleevec was almost immediate. "Even from where I sat, this was a game-changer. It gave us a whole new way to think about how to develop drugs," he said.

Fifteen years ago, it was typical for one or two drugs to be approved annually to treat leukemia. "One year there were three, and I was dancing on my desk," DeGennaro said. Since 2017, thanks to the explosion of precision medicines and immune therapies, there have been 81 drug approvals for blood cancers, he said, 68 of which were at least partially funded by his society.

In addition to working well, Gleevec also can be delivered by a daily pill, instead of hours in an infusion center with terrible side effects.

"Today, a patient doesn't get a death sentence from their physician, they get a prescription," DeGennaro said. "They treat their cancer by taking two pills a day and live a long, healthy productive life."

Good results are good for business

Gleevec and other targeted therapies aren't cures, and they don't work for everyone. Most of the drugs stop working after a while.

But for some patients, including Mann, Gleevec is the only drug they'll ever need to block their cancer. Some people are able to pause the drug for periods of time – DeGennaro recalls a young patient who took two breaks to have babies – while some can eventually stop it altogether.

The fact that it's a long-term therapy means drug companies can make a lot of money, even on relatively rare diseases, said Dr. George Demetri, director of the Sarcoma Center at Dana-Farber Cancer Institute in Boston, who treats relatively rare solid tumors and proved that Gleevec worked for gastrointestinal stromal tumors.

"It changed the economic incentive for biotech," he said.

The quick time frame for approval, with trials started in 1998 and the drug approved in 2001, sped up the pace by which science could help patients, Demetri said.

"I never could have done that in the '90s. Never," he said. "It used to take 20 years to figure out if you had a drug."

Before Gleevec, doctors didn't understand why a drug stopped working in a particular patient. But by focusing on a specific target like the enzyme that Gleevec attacked, it was easier to see when and why a drug became ineffective, Demetri said.

"By fundamentally understanding the mechanism, we can be engineers," he said. "Otherwise, you're just trial and erroring it."

Plus, by showing that cancer care could truly extend patients' lives, rather than just making them miserable with chemotherapy, Demetri said the drug had an "ongoing inspirational impact," encouraging many more talented doctors and researchers to enter the field.

Mann, now 64, tried going off Gleevec, but his cancer threatened to return, so now he's on it for life.

Although some people suffer worse side effects, Mann only has puffy eyes and some fatigue and muscle aches, which he manages by drinking a lot of water and running nearly every day.

Demetri laughs thinking about his gastrointestinal stromal tumor patients complaining now that they don't tan as well while taking the drug, compared to the horrible prognosis he used to talk to them about.

"It's been transformational," he said.

Extra decades of life

Mann found out he was sick at 37, when he went to an Army doctor complaining of back pain. An MRI indicated something was wrong with his bone marrow, and a blood test showed his white blood count was through the roof.

Mann, then a major working on future weapons systems, said he simply couldn't accept his death sentence. His daughter Patrice was still in kindergarten. "Her being 5 gave me a reason to live," he said.

About 18 months after he was diagnosed, while running a bone marrow drive, he met a man with a different type of leukemia. The man told him about clinical trials and said he needed to get himself to MD Anderson in Houston.

Mann did and was in one trial that didn't help much. As his white blood cell count climbed in early 1998, Mann was getting worried. "I was totally out of options," he said, and more than three years out from his diagnosis.

Wasn't there anything else to try? The doctor said there was one trial he was optimistic about, but it hadn't started yet. Mann wasn't sure he'd survive long enough, but when he got the call that summer, he signed on. He swallowed his first dose Aug. 3, 1998.

As the months went by, Mann wasn't seeing much change in himself, but he kept bumping into other trial patients who had joined later and were getting higher doses. They seemed to be thriving. By December, his doctor convinced the company running the trial to give Mann a higher dose. He was lucky to have made it that far. Others didn't last long enough.

"It definitely was my lifesaver," Mann said.

Dr. Brian Druker, an oncologist and researcher at Oregon Health & Science University, in Portland, remembers the first patient ever given Gleevec. Bud Romine, a retired railroad engineer, had reached out to Druker in 1996 after an article ran in the local paper touting the lab research and volunteered.

He was started on an even lower dose than Mann, and it didn't work. But Romine also lived long enough, and by 1999, Druker was able to convince Novartis to let him increase the dose. "He responded beautifully," Druker said, adding that Romine years later died of something other than cancer.

Perseverance delivers

Before Gleevec, treating chronic myeloid leukemia was a challenge for doctors, too. Druker would tell patients they had about three years to live, but he wouldn't tell them how anxious he'd be every time they came in for a checkup.

If their leukemia had switched from the chronic to an acute phase, "it was a time bomb. Game over," Druker said. "At some point it was going to take off and there was nothing you could do to prevent that."

In the early 1990s, treating leukemia patients at Dana-Farber, Druker hoped his research could help improve that outlook.

He was studying a family of enzymes called kinases that drove cell growth. Druker was hopeful that if he could just turn off the one abnormal kinase that was driving chronic myeloid leukemia, he could cut off the fuel supply feeding the cancer and change the outlook for his patients.

But there were 500 such enzymes, and Druker's peers thought if he shut off one, he'd shut off them all and kill the patient.

His career was going nowhere, so he moved to Oregon Health & Science University.

Almost immediately, good luck struck. In Druker's first days on the West Coast, he had reached out to a colleague at a drug company to see if he had any new drug in development that might inhibit the kinase. He did, and Druker showed it worked amazingly well. It killed cancer cells in a lab dish, leaving healthy cells untouched.

But it wasn't so easy to turn a successful lab experiment into a treatment.

Druker is credited with the success of Gleevec in part because of what came next: years of lobbying and arm-twisting to get the drug company, now known as Novartis, to bring the drug to market.

On Friday afternoon, Druker and Mann reunited for the first time in nearly four years.

"I'm so glad to meet my lifesaving hero," Mann said to the box on the Zoom screen.

He thanked the researcher for giving him the chance to watch his daughter grow up. Patrice, now 31, is finishing up a medical residency at a Harvard-affiliated hospital and is getting ready to move back home to Atlanta to work at Emory University.

Druker was clearly moved.

Meetings like that and letters from survivors keep him going, looking for the next transformational therapy or effective drug combination, said Druker, who now directs OHSU's Knight Cancer Institute.

"It reminds me what we've accomplished," he said, "and also what more we have to do."

Contact Karen Weintraub at kweintraub@usatoday.com.

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This article originally appeared on USA TODAY: Life-saving drug Gleevec for leukemia, other cancers 20th anniversary