The survivors: How an experimental treatment saved patients and changed medicine

This is a story of survivors — of patients who were expected to die more than two decades ago but didn’t.

It was the summer of 1998, and Dr. Brian J. Druker was a few months into Phase 1, first-in-human trials of a promising compound that would later be known as Gleevec.

Druker, a researcher at Oregon Health and Science University, knew from lab studies that the drug could disable a gene that controls certain leukemia cells, while leaving healthy cells intact. But he didn’t have answers to a lot of other questions, including what dose would be beneficial.

In an earlier round of testing, patients received a lower dose that failed to stop the spread of their cancer.

In January 1999, a new round of patients, all with chronic myeloid leukemia (CML) drove the wooded, winding road to Druker’s hilltop clinic, with views of Mt. Hood and its surrounding peaks. Like the others before them, these patients sat for repeated blood tests and bone marrow biopsies.

Unlike the others before them, their cancer disappeared. And, for a vast majority, it never came back.

It was just the beginning of an approach known as precision medicine, in which a drug is tailored to an individual patient’s genes and other characteristics. It would be a sharp departure from the scorched-earth approach of standard chemotherapy — and it would open up an entire new field of oncology. Gleevec, the New England Journal of Medicine said last month, was a drug that “changed everything.”

This is an oral history of what happened, and how Druker and three of his longest-surviving patients remember the drug that changed their lives.

Doralee Mortensen (now age 79; diagnosed in 1991): In 1991, I was teaching nursing at Southern Oregon University, a couple hundred miles from Bend, where I live. I was very healthy. I used to bicycle and ski. I got what I thought was the flu. I saw a nurse practitioner and she said we should just see what your [blood] counts are.

In the morning, probably 7:30, I got a call from the doctor. He said, “You need to come in right away.” He said it looked like it was CML. I looked up all the statistics: 80 percent chance of dying in two years, 10 percent chance of dying within six months, 10 percent chance of living to 10 years. Nobody lived past 10 years. And there’s no cure. They put me on interferon [an anti-viral medication that was widely used at that time to treat CML].

Doug Jenson (now age 83; diagnosed in 1997): I was on the maximum dose of interferon almost from day one. I just got sicker and sicker on it. Every day I got up at 6 o’clock in the morning. We had a big thermometer on our porch, and I’d sit there all day and watch it go up, and then go down, and then I’d go to bed. Finally my doctor said the interferon’s killing you faster than the leukemia. We’ll take you off that.

Mortensen: Now it was ’95. My oncologist said you’ve had CML for four years now, and it’s time you look into a bone marrow transplant at OHSU [Oregon Health and Science University, in Portland]. So I talked to a doctor there and he said there’s this guy Druker working on a new drug, but it’s in the test tube phase. Call him. We had a nice conversation and he said to keep in touch. I called him the next year and he was in animal studies, with dogs, I think. Next year I called him again and he said “Well, we’ve run into some liver problems with the dogs we’re testing. It’s slowing us down.”

Dr. Brian Druker: With clinical trials, you’re really appealing to a patient’s altruistic nature, the idea that, “I don’t want anyone to go through what I went through. And if I can help the next person, I’m willing to be a test subject.” But from my own point of view, if I’m talking about a Phase 1 trial, I want there to be at least a glimmer of hope that this might pan out. If it has no chance of working, there’s no altruism there. That’s just masochism.

Judy Orem (now age 73; diagnosed in December 1995): In May of ’97, the Leukemia and Lymphoma Society gave Dr. Druker a grant to help take STI571 out of the Petri dish and into some trials. My good friend heard about it on the radio. She called and said, “Judy, they’ve got another drug they’re working on.” She was in Portland. She connected me with Dr. Druker. He said, “Well, would you like me to put you on the list for when this comes up?”

Jenson: I met Dr. Druker in September ’97. But they weren’t doing people at that time.

Mortensen: I kept skiing and I was working a little. I found that if I kept active, the nausea would go away from the treatments. If you’re physically active, the endorphins kick in and you feel better, even though it’s the last thing in the world you want to do. And I slept a lot. During that time my husband couldn’t handle living with someone that was terminal, so he found someone else. So I was on my own there for a while.

Orem: In June ’98 they did another biopsy and discovered that the interferon wasn’t doing anything. I’d failed everything. My doctor said she thought I had six months before I’d have a blast crisis. And they might be able to keep me alive another year with massive chemo.

Jenson: Finally, my kids and family decided, well, we’d better take a family vacation. So in October ’98, we spent a week at Disney World in Florida. My whole family. Kids and grandkids. We had a ball. And because I wasn’t on the interferon, I felt fine. A little tired, maybe.

Mortensen: In the summer of ’98, Dr. Druker called and said they were starting the Phase 1 study, and I’d be No. 3 on the list. I’d start in August.

Druker: The very first patient was a retired railroad engineer from a small town on the coast of Oregon called Tillamook. He’d contacted me several years before we started the clinical trial. Bud Ramine. He took 25 milligrams a day of what wasn’t even in those days STI571, or imatinib, or Gleevec. Within three to six weeks, his white blood count rose to too high a level for our comfort, so he had to be taken off the study.

Orem: In June of ’98 when I’d failed the other drugs, that was when they started testing STI571 on humans. I was scheduled to go on the trial in January, so the question was whether I’d have advanced too far by then. We as family took a trip to New Zealand in mid-November. Doctors had started me on something to control the platelets, so I had to have blood tests down there too.

Mortensen: After Dr. Druker called and said I could start in August, I talked to my local oncologist. I’d always wanted to go to Tibet. And Phase 1 studies, you die on those. I told my oncologist I want to start on this trial, but I really want to go to Tibet first. He said it’s a great idea. If you go in at No. 3 on the trial, they’ll start you at really low doses, and the odds are it won’t work.

So I went. I hiked and camped out in the mountains and forded streams. I did really well. It was wonderful.

I got back in October. I had to get an apartment in Portland. I had to be within 10 minutes of the hospital for three months. That was the rule. I had a little apartment on the second floor, all by myself. I had my cat with me. Rascal. He was a tabby. It was a lonely time.

I drove myself to hospital. I showed up around 8 o’clock, and they put us in a teeny tiny room. I met Dr. Druker, for the first time, I think. He was tall, thin, kind. He had a wonderful smile and was so encouraging. You just feel like you’re in amazing hands.

There was one nurse who took our blood every day, and at 10:30 in the morning on an empty stomach I took the pill. I was really nauseated. They told me I could take a cracker.

It was scary, but when you’ve tried everything and nothing’s worked, you’re so excited. Everybody that’d gone before me had been kicked off the study because it didn’t work. But I didn’t know that.

We got to know each other. Judy Orem came in in January, and she and I have been close ever since.

Orem: When I talked to Dr. Druker about doing this, he’d said, “If you have any problems, we’ll do whatever we can to get you stabilized again. Because he said it’d really look bad to have you die on the study.” I just felt extreme confidence in him. If he said “jump,” I was going to jump.

I got good results right away. Like in three or four weeks, [the signs of cancer] just started dropping off. I got puffy eyes, which I still have a little. And in the jowls. My eyes water a little. People since have complained about this or that little side effect, but they never did interferon.

Jenson: It was scary for a while. There were 31 people were on the clinical trial when it was filled, and 30 were doing really, really well. The only one that wasn’t was me. So they did a bunch of tests. I’d been on Dilantin [an anti-convulsant medication] because another doctor was worried about possible seizures. So they took me off that and immediately my results improved. Now all 31 people on the drug we were doing well, which, of course, was unheard of.

Druker: I’m looking at this and thinking, “This is amazing. We’ve never seen anything like this before.” These are people who’d been told to get their affairs in order. And now their blood counts are normal. But here’s the problem: When can you celebrate? I felt a little bit like walking on eggshells, because it’s like, “OK, is this going to be a flash in the pan, or is this going to last?” And there’s only one way to find out: wait and see.

Orem: I didn’t think about the sustaining. I just figured it would work.

Jenson: I never asked Dr. Druker how’s so-and-so doing. I thought, “I don’t need to get that stuck in my brain that so-and-so is having a problem or doing better than I am.” My wife and I had had a wonderful marriage and family, and I figured, well, no matter what happens, it’s going to be OK.

Mortensen: I had a dream that I was cured and he [Druker] said, “Dori, it’s working.” But I didn’t really allow myself to think that because nothing had worked.

I had a bone marrow biopsy. I’ve had 70 of them. When they’re drilling through the bone, all you hear is the sound. You don’t feel anything. But when they draw it out, it’s like a dentist hitting a nerve.

It was November 2002 when they called me. They left a voicemail, that I was down to 1 percent abnormal cells. That I would survive. It was – it was – [crying]. Sorry. So I called everybody that I knew. By then I had a man in my life — we’ve since married. We celebrated over lunch.

I felt — I can say this — everybody I’d known had died. All the clinics I’d been to, all the waiting rooms I’d been in, all those people had died. So many had children, young children. One fellow who’d just been married and had a baby and he didn’t survive. I was in a meditation group for terminal patients and I’m the only one in that room of 10 people that’s still alive. And some of it is survivor guilt. Why me?

Obviously, I’m very thankful and feeling very lucky, but it was just so many people had died.

You just kind of think, “I’ve got to live for them.”

The last time I saw Dr. Druker was in November. He said, “You know, you’re the longest in the world living with CML. Twenty-five years. You oughtta have a party.” So I called all the people who’d helped me through this, and we had a great party at my house. I told them about the experience of being diagnosed and how each one of them had helped me in this process. Because you can’t do it alone.

Postscript

Bud Ramine, the first patient to receive the Gleevec dose, was invited to receive a larger dose in 1999, and responded well enough to survive several years longer. He died of an unrelated condition.

Doug Jensen celebrated his 60th anniversary with his wife last year. They have six grandchildren and one great-grandson.

Mortensen married a physician who had lost his first wife to breast cancer.

Judy Orem now represents CML patients in meetings with the Food and Drug Administration. While Mortensen is the longest living CML survivor, Orem is the longest surviving patient continuously on Gleevec. They had never met before the Gleevec trials. They now consider themselves best friends.