A leading-edge immunotherapy may extend survival for patients with one of the most aggressive forms of blood cancer, according to newly published five-year results from a major clinical trial in the journal Blood.

The clinical trial evaluated lisocabtagene maraleucel (liso-cel), a type of chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), a population with historically limited treatment options and poor outcomes after standard therapies fail.

Among 257 patients who received the treatment and were evaluated, investigators observed a median overall survival of 27.5 months, with an estimated 38 percent of patients alive at five years. Disease-specific survival — which excludes deaths unrelated to lymphoma — was a median of 67.8 months, with a five-year rate of 52 percent.

In patients who responded well enough to enter a long-term follow-up study, the five-year overall survival rate reached 78 percent, and disease-specific survival climbed to 92 percent.

CAR T-cell therapy works by collecting a patient’s own immune cells and genetically modifying them to better recognize and attack cancer. In the study, the therapy targeted CD19, a protein found on the surface of B-cell lymphomas.

“The scientific rationale for CAR T therapy was based on the clinical observation that inpatients who had an allogeneic stem cell transplant, meaning from a donor, versus an autologous transplant, meaning your own cells, maintained better control of their underlying malignancy, either lymphoma or leukemia,” said Leo I. Gordon, MD, the Abby and John Friend Professor of Oncology Research and professor of Medicine in the Division of Hematology and Oncology, who was a co-author of the study.  “And we think that the reason for that is that the T-cells from the donor are attacking the lymphoma.”

But donor transplants carried serious risks, including graft-versus-host disease. CAR T therapy was developed to harness the cancer-fighting power of T-cells while avoiding those complications, Gordon said.

“The major focus in this area of research was to develop a T-cell that could circumvent the toxicity but still kill the malignancy,” Gordon said.

The result is a “very activated killer cell that targets the lymphoma cell,” he added, engineered from the patient’s own cells, but enhanced to be both precise and potent.

Diffuse large B-cell lymphoma is the most common and one of the most aggressive types of non-Hodgkin lymphoma, according to the Lymphoma Research Foundation. While many patients are cured with first-line chemotherapy, about 30 percent relapse. For those who don’t respond to additional treatments, outcomes have historically been grim.

“In the third line, after patients had already had a transplant and progressed, there were very limited options,” Gordon said.

The new study shows that outcomes improve dramatically once patients pass the early high-risk period, according to the authors. Most deaths occurred within two years of treatment, and relapses after that point were uncommon.

“What we’re seeing is that beyond two years, the chances of a relapse are very low,” Gordon said. “In that group of patients, it’s considered to be a curative therapy when there were previously no other options.”

Even when looking at all treated patients, roughly half were alive without disease, far exceeding historical expectations for this population, Gordon said.

Additionally, the study found no new safety concerns with longer follow-up. Rates of severe late infections and second cancers remained low, easing concerns about delayed toxicity, a key question for therapies that permanently alter the immune system.

Gordon and his collaborators are now exploring whether CAR T therapy could replace or precede chemotherapy in certain high-risk patients, potentially improving cure rates even further.

“Should this be the only treatment people get instead of chemotherapy? That is a legitimate question,” Gordon said.

Scientists are also working to refine the technology itself. Next-generation approaches include targeting multiple cancer markers simultaneously, enhancing T-cell durability and even developing “in vivo” CAR T therapies where the genetic modification occurs directly inside the patient’s body rather than in a lab.

Beyond lymphoma, the technology is expanding into other cancers and even autoimmune diseases such as lupus, with early results showing promise.

“This is really in its infancy,” said Gordon, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “It’s a very exciting time in oncology and in the study of immune diseases.”

The study was supported by Juno Therapeutics, a Subsidiary of Celgene.