‘You won the lottery’: The very first CAR T cell patient
After Alison Loren, MD, delivered the news to Bill Ludwig that his body was free of leukemia, he lay down in his bed in the Hospital of the University of Pennsylvania, looked around the room, and let the doctor’s words sink in.
After an hour, he walked out to the nurses’ station. “Has Dr. Loren been on this floor this morning?” he asked. She had checked in with them on her way to his room, the nurses said. “She didn’t see you?” they asked.
“Oh yeah, she saw me,” he said. “I was just making sure that I remembered it correctly. Because I could be hallucinating.”
But this time, he wasn’t. After weeks of chaos—fevers and chills, hallucinations, legs swelled up to three times their size, he had ended up in the intensive care unit. But now his oncologist, Loren, delivered this good news. It was the chimeric antigen receptor (CAR) T cells that had sent his immune system into cataclysmic overdrive, and they had been doing their job all along: finding his B-cell chronic lymphocytic leukemia (CLL) and destroying it. Five and a half pounds of cancer were wiped out in less than a month.
Ludwig would forever be known as the first person to be successfully treated with a cellular therapy designed to hunt down and kill cancer cells with his own immune system.
“I’m looking for [extending life by] a day, a week, or a month, and here they are telling me I don't have cancer,” Ludwig said. “It was just like someone told you, ‘You won the lottery.’”
The journey to a first-of-its-kind clinical trial
It had been an arduous, nearly 10-year path to get to this unprecedented result. Diagnosed with CLL in early 2001, Ludwig spent the better part of that decade undergoing round after round of different chemotherapies that ultimately stopped working. He didn’t qualify for a bone marrow transplant. And a clinical trial at the National Institutes of Health in Bethesda, MD, proved fruitless for him. In early 2010, he found himself back at HUP under Loren’s care, and seemingly out of options.
That's when she brought up an experimental therapy from the team led by Carl June, MD.
“[Penn] had kept me alive for nine years. They needed someone to go into a clinical trial,” Ludwig said. “Why not?”
He received his first infusion on Tuesday, Aug. 3, 2010. Two others followed that week. Then the chaos ensued that sent him to intensive care. But initially, no one was sure what was happening to him.
“This was brand new territory and we didn’t know what to expect,” said David Porter, MD, director of Blood and Marrow Transplantation in the Abramson Cancer Center, and a clinical leader on the CAR team. “And he was getting sicker, and I will freely admit that I was convinced he had pneumonia.”
Researchers would later discover that the billion engineered T cells placed back in Ludwig’s body grew to a trillion and went on a war path to kill his B cells. All the symptoms his body had experienced were the casualties from that all-out attack. It's called cytokine release syndrome.
The joy of recovery, followed by years of remission
The elation when he started getting better, and you realize that his leukemia is rapidly disappearing is incredible,” Porter said. “You start becoming a little more convinced that the illness period really did have something to do with the T cells, and it wasn’t an infection.”
Not one, but two bone marrow biopsies showed no sign of cancer cells, and his lymph nodes now appeared normal sized on an X-ray. This was the news that Loren delivered in the aftermath of Ludwig's three-week ordeal.
Back from the nurses’ station, Ludwig waited for his wife, Darla. “She walked in and I told her,” said Ludwig, his voice cracking. “We just hugged each other. And we both cried.”
The next day, they left the hospital.
That was seven and a half years ago. Ludwig remains in remission and in good health, enjoying each day with Darla, their kids, and their kids’ kids, traveling around the country in their RV or just being at home.
“I know it's a cliché, but everything’s precious,” said Ludwig, now 72 and retired from his career as a corrections officer. “I just keep thinking of the things that I would have missed… seeing granddaughters in college and watching grandsons grow up.”
There’s profound gratitude and emotion in Ludwig’s voice when he talks of his experience at Penn—and everything that has unfolded with the “living drug" since.
After Ludwig, over 330 more adults (and counting) would go onto be treated with CTL019 therapy at Penn. His trial also paved the way for the clinical trials in children and young adults with acute lymphoblastic leukemia (ALL) that ultimately led to the therapy's approval.
In a way, he went along on that journey.
He remembers crying—“like a baby”— in his living room watching NBC’s Nightly News when they featured the story of Emily Whitehead, the first child to successfully be treated with CTL019 at Children’s Hospital of Philadelphia. He’s thankful to have met Doug Olson, the other patient who had a complete response to the therapy in 2010 and remains well today, and others whose lives were saved or improbably extended by the therapy, when attending a 2013 ceremony where June and his team received the Philadelphia Award.
And when he found out the therapy had been approved by the Food and Drug Administration—via a Facebook post from his daughter—he was overwhelmed with excitement, mostly over what’s to come.
“Hopefully there is no end to the cancers that ultimately the immune system will be able to eliminate,” Ludwig said. “Let’s hope this is the beginning of something large that maybe future generations will take for granted.”
Editor’s note: After this story was initially published in 2018, Ludwig continued to travel and enjoy the company of his family, remaining active in long-term remission from cancer for more than a decade after his CAR T cell treatment. He died of complications of COVID-19 in early 2021.