Sustained results with a CAR T-cell therapy for an aggressive blood cancer

When chemotherapy stops working and stem-cell transplantation fails or is not an option, medicine has little to offer patients with the aggressive blood cancer called diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma. But that could be changing.

New clinical trial results at OHSU and 26 other study sites around the world show high rates of durable responses to treatment with a CAR T-cell therapy. CAR stands for “chimeric antigen receptor” and the treatment is a form of immunotherapy in which the patient’s immune system T cells are collected, genetically engineered to target cancer cells then infused back into the patient. The study treatment, tisagenlecleucel (brand name: Kymriah), targets CD19-expressing B cells.

Richard Maziarz, M.D., medical director of the adult blood and marrow stem cell transplant and cellular therapy program in the OHSU Knight Cancer Institute. (OHSU/Kristyna Wentz-Graff)

At a median of 19 months after infusion, the overall response rate was 54 percent among 99 trial participants who were followed for at least three months or discontinued therapy early. Among responders, 40 percent achieved a complete response, and 16 percent achieved a partial response. Data from the Phase 2 JULIET clinical trial, led in part by OHSU’s Richard Maziarz, M.D., was just presented at the ASH meeting in San Diego.

“This study is the first to outline long-term Kymriah results for these lymphoma patients, and we’re seeing that these responses can be sustained,” said Maziarz, senior investigator for the clinical trial and medical director of the adult blood and marrow stem cell transplant and cellular therapy program in the OHSU Knight Cancer Institute.

“There are a significant number of patients who are remaining free of disease, and none of those still in remission proceeded on to transplantation,” he said. “This approach appears to offer a single treatment that can relieve symptoms and save lives for people who had otherwise faced a very poor prognosis.”

The dangerous toxic effect known as cytokine release syndrome occurred in more than half of those receiving CAR T-cell infusions. It was controlled without causing any deaths in the clinical trial, researchers reported in a New England Journal of Medicine paper published online to coincide with the ASH meeting presentations on the JULIET trial.

Some 30 percent of trial participants were unable to receive an infusion, mostly as a result of disease progression or death, the authors reported. They said limited manufacturing capacity at the start of the study was a big factor, and that this logistic problem can be managed to enable a larger proportion of patients to receive CAR T-cell treatment before their disease progresses.

Read more at OHSU News.