CAR T-cell therapy shows significant remission rates for those with aggressive B-cell lymphoma

A study involving the recently approved CD19-targeting chimeric antigen receptor (CAR) T-cell therapy shows that 42% of patients with aggressive large B-cell lymphoma remained in remission at 15 months following treatment with axi-cel.

The study, named ZUMA-1, also reported measurable responses in 82% of patients and complete responses in 54%. Fifty-six percent were alive at 15 months following therapy, with some remaining cancer free two years post-treatment. 

The findings were reported in the Dec. 10 online issue of The New England Journal of Medicine, and presented at the American Society of Hematology’s (ASH) Annual Meeting and Exposition this past December. They resulted from a 22-institution study led by Sattva Neelapu, M.D., professor of Lymphoma and Myeloma at MD Anderson, and Frederick Locke, M.D., vice chair and associate member of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center. 

“With the FDA’s recent approval of this therapy, we believe this is a major advance in the treatment of patients with relapsed or refractory large B-cell lymphoma, and is likely to save or prolong lives of many patients,” says Neelapu. “This study demonstrated that axi-cel provides remarkable improvement in outcomes over existing therapies for these patients who have no curative options.”

In CAR T therapy, a person’s own T cells – disease-fighting immune cells – are removed and sent to a lab where they are genetically re-engineered to produce chimeric antigen receptors (CARs) on their surface. CARs are proteins that allow T cells to recognize cancer.

The CAR T cells are then multiplied in the laboratory until there are millions. Next, they’re sent to the hospital and infused back into the patient’s bloodstream. These “attacker” cells not only recognize and kill cancer cells, but they may remain in the body long after the infusion has been completed and guard against cancer’s recurrence.

The study, which began in April 2015, administered axi-cel to 108 patients who had failed prior chemotherapy and autologous stem cell transplantation. In some cases, the patients who had received chemotherapy were too far progressed to undergo stem cell transplantation and were placed on the trial following chemotherapy.

“This is the first FDA-approved gene therapy to treat adult lymphoma,” says Locke. “Many patients’ lymphoma tumors melted away within a month. The long-term follow-up results of the ZUMA-1 trial show that axi-cel remissions can last for years, and these are patients who did not respond to chemotherapy.” 

Proud to be a clinical trial trailblazer 

In 2013, Emily Dumler was diagnosed with a type of non- Hodgkin’s lymphoma called diffuse large B-cell lymphoma. After chemotherapy and an autologous stem cell transplant failed to stop her cancer, she qualified for the final spot in Sattva Neelapu’s study of CAR T-cell therapy for lymphoma. 

“I felt grateful just to have another option – a really viable one that my doctors were excited about,” Dumler says. “And for the first time in a long time, I actually felt hopeful.” 

Dumler was only the second patient at MD Anderson and the third in the world to receive CAR T cells to treat non-Hodgkin’s lymphoma on the multicenter clinical trial. She battled what is known as cytokine release syndrome and neurological side effects, both common to CAR T-cell therapy, but quickly recovered. A month after her infusion, tests showed her cancer was in complete remission. Two and a half years later, she remains cancer free. 

The experience not only changed Dumler’s life, it changed the way she views clinical trials. 

“Before I was on a clinical trial, I felt sorry for patients participating in them. I considered clinical trials a last-ditch effort,” Dumler says. “But knowing that I was a trailblazer in this area makes me feel so proud. Clinical trials are the future of medicine. And they really are how new treatments become available.”