Axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor (CAR) T cell therapy that targets CD19-expressing cancer cells, elicits durable responses in a substantial portion of patients with aggressive large B cell lymphoma, a recent multicenter phase I/II trial has shown.
In the trial, named ZUMA-1, patients with treatment-refractory large B cell lymphoma received axi-cel as a single intravenous infusion following a conditioning regimen of low-dose cyclophosphamide and fludarabine. In an analysis that included all 108 patients treated in either phase of the trial, the objective response (complete and partial responses) and complete response rates were 82% and 58%, respectively, at a minimum follow-up of 1 year. At the data cutoff date, with a median follow-up of about 15 months, 42% of patients continued to have a response, with 40% having a complete response.
Twenty-three patients who had either a partial response or stable disease at their first assessment 1 month after axi-cel treatment had complete responses that occurred as late as 15 months after treatment. The 15-month overall and progression-free survival rates were 56% and 41%, respectively. Three of the seven patients treated in phase I of the trial had ongoing complete responses 2 years after treatment.
Grade 3 or higher adverse events occurred in most patients and included fever, infections, leukopenia, thrombocytopenia, and anemia. In addition, most patients experienced cytokine release syndrome; although the majority of these patients had low-grade cases, two patients died of adverse events related to cytokine release syndrome. Many patients also experienced neurological events, which tended to appear about 5 days after treatment but resolved within about 15 days.
“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 the lives of many patients,” said Sattva Neelapu, M.D., a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. Dr. Neelapu was a co–first author of the study’s report, which was published in The New England Journal of Medicine (2017;377: 2531–2544) and presented at the 2017 annual meeting of the American Society of Hematology. “This study demonstrated that axi-cel provides remarkable improvement in outcomes over existing therapies for these patients who have no curative options,” he said.
In October 2017, the U.S. Food and Drug Administration approved axi-cel for the treatment of relapsed or refractory diffuse large B cell lymphoma.
OncoLog, March 2018, Volume 63, Issue 3