A study published in the Journal of Clinical Oncology confirms that one of the first Food and Drug Administration-approved CAR-T cell therapies offers long-term survival and potential cures for adult patients with relapsed or refractory large B-cell lymphoma, even years after treatment.
CAR-T cells are genetically engineered immune cells that target cancer.
Oregon Health & Science University has been involved in the drug's clinical trials and its subsequent FDA approval since 2014, when Richard Maziarz, M.D., former medical director of the adult blood and marrow stem cell transplant and now leader of the immune effector cellular therapy program in the OHSU Knight Cancer Institute, was named as co-principal investigator of the trial, along with Stephen J. Schuster, M.D., of the University of Pennsylvania.
"This is the final, long-term analysis of the JULIET trial — one of the earliest CAR-T studies in the U.S.," Maziarz said.
"We're now identifying many survivors six years out, which is remarkable for a population that had very few options and very limited expectations for any meaningful survival."
OHSU has been a pioneer in CAR-T cell therapy, leading this foundational clinical trial and shaping its design and rollout—from when CAR-T patients were in the tens, to now, when they're in the thousands.
"This clinical trial is foundational to CAR-T cell therapy, and just one example of OHSU's long and growing history of exemplary cancer research and patient care," said OHSU President Shereef Elnahal, M.D., M.B.A. "We are honored to do the work that offers hope to people battling lymphoma, and indeed any cancer, here in Oregon, across the country, and across the world."
'The living drug'
The JULIET trial, launched around 2014, led to the approval of Novartis' chimeric antigen receptor — known as CAR-T-cell therapy tisagenlecleucel, marketed as Kymriah, for adult patients with relapsed or refractory large B-cell lymphoma. Participants had failed at least two previous lines of systemic therapy.
The first CAR-T cell gene therapy available in the U.S., Kymriah uses CAR-T cell therapy, a form of immunotherapy in which the participant's own blood cells are collected, genetically engineered to attack B-cell lymphoma cells, then infused back into the patient.
In the new study looking at longitudinal results, of the 115 participants infused, the five-year overall survival rate reached approximately 32% and was 56% among patients who achieved a response.
"In a group where historical survival was projected to be under 5% to 10% at five years, we're now seeing clear evidence of long-term, durable remissions," Maziarz said. "We're not just talking about temporary responses anymore. We're talking about remission for more than five years in a disease that was once considered incurable at this stage."
The study also demonstrated that CAR-T cells remained detectable in the blood of some participants more than five years later, supporting the therapy's long-term persistence and effectiveness, and as well proof of principle that CAR T-cell treatments are appropriately nicknamed "the living drug."
Maziarz emphasized OHSU's pivotal role in the trial.
"We helped enroll and follow participants, and, importantly, I served as chair of the original scientific steering committee, alongside colleagues from the U.S. and Europe," he said. "We shaped this trial from its design to its global rollout."
Foundational study
Since the JULIET trial, the CAR-T cell therapy landscape has expanded dramatically.
"At the time of this original study, fewer than 100 people a year were getting CAR-T in the U.S. Now, it's approaching 6,000 annually," Maziarz said. "This was the foundational study that helped make that growth possible."
The research also identified key biological markers that could help predict who is most likely to benefit from CAR-T cell therapy.
"It's not just about giving the drug anymore — it's about matching the right therapy to the right patient at the right time," he added.
Looking ahead, Maziarz said efforts are underway to move CAR-T cell therapy even earlier in the treatment process, potentially into first-line care for high-risk disease.
"We're exploring how to identify those at greatest risk of recurrence and intervene with CAR-T cell therapy before the disease becomes unmanageable," he said.
Recent studies from Maziarz and colleagues also show that access to these life-saving CAR-T cell therapies remains a challenge, particularly for lower-income and rural communities.
"This isn't just about treating cancer anymore," he said. "We've changed the natural history of the disease. And now the challenge is making sure everyone who needs this therapy can receive it."
The research was supported by industry partner, Novartis.
