In 2006, Stephanie Florence, a photographer from Idaho, was diagnosed with follicular non-Hodgkin lymphoma.
She was treated with R-CHOP, a common lymphoma regimen consisting of the drug rituximab (Rituxan) and several chemotherapy meds.
When her cancer recurred seven years later, it had transformed into a more aggressive lymphoma. She subsequently received a stem cell transplant.
When she fell out of remission six months later, she had run out of options. Her situation was dire.
But Florence, 44, had been relentlessly researching what was available in experimental clinical trials. She chose to enroll in a trial for chimeric antigen receptor T cell therapy.
Better known as CAR-T, the treatment is a promising immunotherapy that engineers the body’s T cells to fight cancer.
In this process, T cells are extracted from the patient and genetically engineered with so-called CD19 receptors to seek out cancer cells.
Then the population of the engineered cells is expanded and infused back into the patient, where they go to work against the cancer.
“I knew about CAR-T for two years before the trial,” said Florence.
In July 2015, she was re-infused with her own engineered T cells at the Seattle Cancer Care Alliance. Within weeks she was in complete remission.
Florence has been cancer-free for the past 18 months. And doctors expect it to last.
“I feel better than I’ve felt in years,” Florence said.
She adds that her oncologist, Dr. David Maloney, Ph.D., a cancer researcher at Fred Hutch in Seattle, and his team are “very encouraged by my success.”
Juno Therapeutics, a Seattle-based biopharmaceutical company, oversaw the clinical trial.
Juno has enjoyed early success with CAR-T as have other companies.
They include Kite Pharma, the California-based company that could be the first to bring this treatment to U.S. cancer clinics in 2017.
Kite’s leading CAR-T therapy, KTE-C19, is for patients with non-Hodgkin lymphoma who do not respond to chemotherapy or whose cancer returns after an autologous stem cell transplant.
So far, it has impressed the scientists.
In the first phase of the trial, 43 percent of participants were still in remission a year after being treated.
“Patients with aggressive non-Hodgkin lymphoma have a major unmet need in terms of available therapies that can induce long-term remission, and there really has been no new treatment for these patients for over 20 years,” Dr. Sattva Neelapu, the lead study author, and a faculty member in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, said in a statement.
He added that KTE-C19 could “potentially be the solution to that need, and the hope is that this treatment option could be curative for some of these patients.”
Other companies also showing impressive numbers in CAR-T trials include Novartis and Bluebird.
The results for CAR-T have given new hope to people with leukemia and lymphoma who have run out of treatment options.
But even with increasing talk of this therapy being a cure for some cancers, there have been setbacks.
In July, Juno executives announced that two participants in its ROCKET trial for people with relapsed acute lymphoblastic leukemia (ALL) had died from brain swelling.
People in the CAR-T trials were informed of the risks, which include a dangerous and possibly fatal side effect called cytokine release syndrome.
The deaths made headlines and the trial was halted.
“This is a humbling experience,” Hans Bishop, Juno’s chief executive officer, said in a conference call last summer. “No doubt it is difficult for the physicians who are looking after these patients and their families. Clearly these therapies are potent, that’s why they offer the potential for cures.”
At the time, Dr. Otis Brawley, chief medical officer for the American Cancer Society, told Healthline he did not think it was a huge setback for CAR-T.
“This kind of thing happens,” he said. “It’s unfortunate, but it happens.”
After Juno removed one of the chemotherapy drugs used in the trial as a pre-conditioner to CAR-T, the FDA allowed Juno to resume its trial.
However, after two more patient deaths last month, the trial was halted indefinitely.
Bishop told Healthline that the company is now sifting through all its collected data on the ROCKET trial in search of answers as to why these two people died.
“We will not resume the ROCKET trial until we get to the bottom of this,” Bishop said. “This is our number one priority. We’re looking at trial results day and night.”
Continuing the trials
While Bishop said there is “no timeline” for resuming the trial, he remains a steadfast supporter of CAR-T.
And there are other trials both at Juno and other U.S. drug companies that have seen successful responses and no deaths.
In fact, amid the uncertainty over the ROCKET trial, Juno announced earlier this month at the American Society of Hematology (ASH) conference in San Diego that 60 percent of people with aggressive non-Hodgkin lymphoma who enrolled in the trial that gave Florence her remission still had no signs of cancer one month into the trial.
And in this trial, there have been no deaths and minimal adverse events, Bishop told Healthline.
Florence said she was willing to take the risk, given the potential benefit and the fact that she essentially had no other choice.
“The clinical trial deaths are of course upsetting to me,” she said. “I knew going in that I could be one of them. But I also knew that they were having successes, and the only way long-term that they can get to a point where they have more success is to continue to have patients enroll in these trials.”
Putting patients first
At Kite and Juno, two of the CAR-T space’s leaders, the chief executive officers of each company, say they are motivated by saving lives.
Dr. Arie Belldegrun, Kite’s chief executive officer, is an oncologist who has established several biotech companies including Kite, Agensys, and Cougar Biotechnology.
He still sees people with cancer every Thursday in his clinic at the University of California, Los Angeles (UCLA).
“It fulfills me more than anything else,” he said.
He adds that passion for helping cancer patients is the reason he founded Kite, where clinical trials are showing successful results for B cell cancers.
“We have a good, solid product,” he said. “We are focused.”
Belldegrun said the company believes so strongly in its product that it has already completed construction of a state-of-the-art manufacturing center in Southern California.
So now, when the treatment receives its first approval from the Food and Drug Administration (FDA), likely in early 2017, Kite can hit the ground running and get it to people who need it.
Juno moving forward
Juno executives are also moving forward.
The company provided funding for a new immunotherapy clinic that just opened at the Fred Hutchinson Cancer Research Center in Seattle.
The Bezos Family Immunotherapy Clinic, named for a family that has been committed to advancing immunotherapy, will allow researchers to conduct twice as many immunotherapy trials in the next year in pursuit of cures for cancer.
Patients will be able to receive the center’s immunotherapies for cancer at roughly double the capacity that existed before the 9,222-square-foot clinic opened.
Intensive monitoring at the facility will enable researchers to better understand why some patients respond while others do not. It also will help achieve the goal of developing the best approach to treatment for each person.
“From our perspective, the clinic is important for a few reasons,” Bishop said. “The basic science of immunotherapy is moving quickly, and the clinic was designed to empower researchers to advance the clinical care of patients at the same pace."
Bishop said that ongoing CAR-T trials “have highlighted the opportunity to improve immunotherapies and patient outcomes, and the clinic will bolster these efforts and ultimately help move these therapies into the clinic more quickly.”
Honoring a patient
Like Kite’s Belldegrun, Bishop doesn’t hesitate to share his passion for helping patients.
He said he named the ROCKET clinical trial after an ALL patient who was a musician and whose nickname was “The Rocket.”
“She had been through all of her options when she found the trial at Fred Hutch,” Bishop explained. “She and her husband moved to Seattle, she received treatment with CAR-T cells and went into a complete remission.”
These were the early days of CAR-T, Bishop explained, and doctors advised her that she should also have a bone marrow transplant.
“She did so, while in remission, and died from complications from the procedure, even though she was cancer-free at the time,” said Bishop.
He said naming the trial for her “reminds us of the very difficult circumstances patients often find themselves in with this and other blood cancers, and inspires us to work to find better treatment options for them.”
Bishop said he was “overwhelmingly encouraged” by the recent results of the non-Hodgkin lymphoma trial.
Despite some negative press this year, he said the company has received widespread support from both investors and patients since the ROCKET trial was halted.
“We want to give patients more and better choices,” he said. “I am truly humbled by all that has happened. But two years ago, all we were talking about was the cytokine release issues. Now we are talking about the results in clinical trials.”
Meanwhile, Florence said doing the CAR-T trial was the best decision of her life.
“I wasn't thrilled with what they were explaining to me about the side effects,” she said. “But with big risk comes big reward. I looked at the end game. I had accepted my mortality at this point. If it happened while advancing treatment options, I had come to terms with that. And in my personal experience, the trial was uneventful and boring. I was expecting all those side effects. I believed the cytokine release correlated to what my response was. There were no side effects, so I did not think anything was happening. I was afraid it wasn’t working. But it was. I am still cancer-free 18 months later.”