medwireNews: Heavily pretreated adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) respond well to treatment with the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel, show results of the pivotal JULIET trial.
The findings, which were simultaneously published in The New England Journal of Medicine and presented at the 60th American Society of Hematology Annual Meeting in San Diego, California, USA, indicate that “tisagenlecleucel shows promise” for DLBCL patients who are ineligible for, or relapse after, hematopoietic-cell transplantation and have “very few treatment options,” say Stephen Schuster (University of Pennsylvania, Philadelphia, USA) and co-authors.
Among the 93 patients who received a single infusion of tisagenlecleucel manufactured at a central facility in the USA, 40% had a complete response and 12% had a partial response, giving an overall response rate of 52% during a median 14 months of follow-up. All patients had previously been treated with least two lines of therapy, including rituximab and an anthracycline.
The median duration of response has not yet been reached, say the researchers, but they note that durable responses could be detected up to 18.4 months after infusion, and they estimated that 65% of responding patients, and 79% of those with a complete response, would remain relapse-free at 12 months after attaining a response.
The estimated progression-free survival at 12 months was 83% for patients who had a complete or partial response at 3 months, while the estimated overall survival at 12 months was 49% among all patients and 90% among those with a complete response.
The safety analysis, which included an additional 16 patients who received tisagenlecleucel manufactured in Europe, showed that cytopenia lasting more than 28 days was the most frequent grade 3 or 4 adverse event of special interest, occurring in 32%, followed by cytokine release syndrome (22%), infection (20%), febrile neutropenia (15%), and neurologic events (12%).
“Adverse effects such as cytokine release syndrome can be severe or even life-threatening; however, they were managed in most patients with supportive measures and cytokine blockade,” Schuster et al remark.
Indeed, grade 3 or 4 cytokine release syndrome occurred a median 4 days after infusion, but 97% of cases had resolved by data cutoff, the team notes.
There were three deaths due to disease progression within 30 days after infusion, and no postinfusion deaths were attributed to the study drug, cytokine release syndrome, or cerebral edema.
Schuster and team conclude: “The high and durable response rates observed with tisagenlecleucel treatment are promising.
“However, it should be noted that follow-up is short, and the potential for long-term toxic effects requires further analysis.”
By Laura Cowen
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