A landmark clinical trial using the measles virus to fight cancer brings patient and benefactors together in an unexpected way
By Mayo Clinic Staff
For some, serendipity is evidence of God's handiwork and divine intervention at times of need. Others take the viewpoint that there are no "accidents" and life events are predetermined by the blueprints of fate. The more scientific-minded may simply chalk it up to the laws of probability.
So when a scientist who has spent his life dealing with facts suddenly stays up all night thinking about God, the universe and destiny, you know something big has happened.
Something science can't explain.
10 years and counting
Stacy Erholtz had been fighting multiple myeloma, a blood cancer, for 10 years.
"For the longest time, my local doctors couldn't figure out what was wrong with me," she says. "I suffered extreme exhaustion. I fell and broke my back. I had two carpal tunnel surgeries. I was nauseated all the time and lost a ton of weight."
She was so sick that she canceled a trip to Denver celebrating her 40th birthday with family. "I had calluses on my knuckles because the only way I could climb stairs was by crawling."
When Stacy came to Mayo Clinic, Stephen J. Russell, M.D., Ph.D., and the myeloma team treated her with a number of therapies — traditional chemotherapy, stem cell transplant, novel anti-myeloma drugs. Each beat back the cancer for a while, but it always returned.
Once while in remission, Stacy and her husband saw Dr. Russell on the local news talking about his measles virus study. Turning to her husband, Stacy said, "I already let Dr. Russell know that if my cancer comes back, I want to enroll in that study."
In time, Stacy's cancer did return. While meeting with her team of physicians at Mayo Clinic, she inquired about the measles study but learned she didn't qualify.
"You have to be the biggest loser first," Stacy says. "I needed to fail every type of treatment available before I could qualify for the study." Stacy still had options — a novel drug combination, then another stem cell transplant using her previously harvested stem cells. She endured months of a compromised immune system, extreme exhaustion and nausea as her bone marrow slowly rebuilt itself.
By the time Stacy was rebounding from her second stem cell transplant, her cancer was already returning. Within months she was accepted into the measles virus clinical trial.
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A virus that beats cancer
Dr. Russell, the Richard O. Jacobson Professor of Molecular Medicine, began researching the cancer-fighting potential of the measles virus more than 17 years ago. At that time, the best evidence suggesting it might work was that a doctor in Africa had reported a facial tumor of a child with lymphoma temporarily receded after he contracted measles.
Researchers have found that even though cancer cells can freely proliferate, they cannot ward off infection as easily as healthy cells can. Today, scientists can create viruses that are too weak to damage healthy cells but are strong enough to destroy tumor cells.
Mayo Clinic Cancer Center is the first institution to successfully use an engineered measles virus as a cancer therapy, including treatment of ovarian cancer and glioblastoma multiforme, the most lethal brain tumor. In 2006, Dr. Russell and his colleague Angela Dispenzieri, M.D., started a clinical trial to infuse multiple myeloma patients with the modified measles virus.
When Stacy entered the study in 2013, she had multiple tumors on her clavicle, sternum, vertebral body and skull. The tumor on her forehead, which Stacy's children named Evan, had grown to about the size of a golf ball and destroyed the bone of her skull, compressing her brain.
A day and a half after Stacy received an infusion of the cancer-fighting measles virus, Evan began to disappear.
Two weeks after her treatment, Stacy couldn't remember feeling so good for so long — "My energy quadrupled."
Seven weeks after therapy all her tumors and any signs of cancer were gone.
Over the years, researchers have reduced single tumors with the measles virus, but Stacy is the first person to go into complete remission after having cancer spread throughout the body.
She is the second person in the study, and the world, to receive the modified measles virus at the highest possible dose of 10 to the 11th power (hence her participant number of 11.2). After her infusion, Stacy learned she received enough of the virus to vaccinate 10 million people against measles. "I might have been scared going into it if I'd known that," she says with a laugh.
Stacy is the first person in history to have had such a remarkable response, providing hope for a powerful new therapy for cancer.
"This study is a milestone for the whole field of oncolytic viral therapy," Dr. Russell says. "Not only because of Stacy's remarkable response, but this is the first study to prove that a virus can target cancer that is widely disseminated throughout someone's body."
So when Stacy was invited to tour Dr. Russell's lab on Sept. 13, 2013, four months after she received her infusion, it was a historic visit. But what happened at the lab is something no one can explain.
"Walking into Dr. Russell's lab was like a Willy Wonka experience," Stacy says. "I got to see behind the scenes and meet the people who are dedicating their life's work to cure cancer with viruses." Among handshakes and hugs, Stacy and her mom met with Dr. Russell's team and posed for pictures.
At one point, Dr. Russell asked Stacy to pose with him by the plaque honoring Mary Agnes and Al McQuinn, the benefactors who made his research with the measles virus possible. After the picture was snapped, Stacy looked at the plaque and exclaimed, "Mary Agnes and Al McQuinn ... I know those people! I was friends with their son."
Stacy knew their son Charles through her work. And the McQuinns own a lake home just up the road from Stacy, so their paths crossed many times. "I just couldn't believe it," says Dr. Russell. "These things just don't happen."
Mary Agnes and Al McQuinn are longtime contributors to Mayo Clinic. In 2005 they were first introduced to Dr. Russell's work with the measles virus and have consistently supported his study ever since.
"This study would not be possible without the McQuinns," Dr. Russell says. "Their support is the reason we will be able to turn our research into treatments to help patients like Stacy."
Dr. Russell and his team provided the McQuinns regular research updates and milestones throughout the study. When patient number 11.2 had a remarkable response, the McQuinns were some of the first to know.
So it's understandable that Mary Agnes's heart fluttered with excitement as she dialed the phone number left on her voicemail with the message: "Hello, Mr. and Mrs. McQuinn. This is patient 11.2. Please call me. I would love to talk with you."
Both Mary Agnes and Al were astonished that after all their years of support, the first really successful patient in Dr. Russell's study was someone they knew. "It is truly miraculous," says Mary Agnes.
Stacy and Mary Agnes spent a long time on the phone talking about the study and their intertwined lives and knew they had to get together in person. Soon the McQuinns, along with their daughter and son-in-law, met Stacy and her mom for brunch.
"We had so much fun celebrating," Stacy says. "We chatted for hours."
Evan's return and demise
In January 2014, Evan, the lump on Stacy's forehead, started to return. It was cancerous, but for the first time in her 10-year battle, it was localized. Dr. Russell and his team successfully treated it with radiation therapy, and there are no other signs of cancer in Stacy's body.
It's been 10 years since Stacy was diagnosed with cancer and had to cancel travel plans to Denver in celebration of her 40th birthday. She made that trip for her 50th birthday.
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