Author: By Shreeya Nanda, Senior medwireNews Reporter
medwireNews: Treatment with the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel is associated with high response rates among adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), shows the pivotal JULIET trial.
These results were simultaneously published in The New England Journal of Medicine and reported at the 60th American Society of Hematology Annual Meeting in San Diego, California, USA.
“Patients with relapsed or refractory DLBCL who are not eligible for high-dose therapy and hematopoietic-cell transplantation or for whom such therapy was not successful have very few treatment options”, write lead author Stephen Schuster, from the University of Pennsylvania in Philadelphia, USA, and colleagues.
“For these patients, tisagenlecleucel shows promise that will need to be confirmed through larger studies with longer follow-up.”
In the phase II study of DLBCL patients who had received two or more prior lines of therapy, including rituximab and an anthracycline, and who were either ineligible for or had relapsed following autologous hematopoietic stem cell transplantation, 111 received a single infusion of the anti-CD19 CAR T-cell therapy. Of these, 95 participants received tisagenlecleucel manufactured in the USA and the remaining 16 were treated with tisagenlecleucel produced in the European Union.
At a median follow-up of 14 months from infusion, the overall response rate was 52% in the efficacy analysis set, which comprised 93 patients who received US manufactured product and had been followed up for at least 3 months at data cutoff. The responses were complete in 40% of patients and partial in 12%.
The median response duration was unreached at the time of analysis, as was the median progression-free survival among patients with a complete response. Overall survival was a median of 12 months for the 111 trial participants.
The researchers estimate that 65% of the responding patients will remain relapse-free at 12 months, while 83% of those with a complete or partial response at 3 months will be progression-free at the 12-month mark.
With regard to the safety profile, the most common grade 3–4 adverse event of special interest during the initial 8 weeks after infusion was cytopenia unresolved at day 28 (32%), followed by cytokine release syndrome (22%), infection (20%), febrile neutropenia (15%) and neurological events (12%).
Stephen Schuster and co-authors note that most of the incidences of grade 3 or 4 cytokine release syndrome had resolved at data cutoff, and no deaths were deemed related to tisagenlecleucel treatment, cytokine release syndrome or cerebral oedema.
They add: “By monitoring the patients for fever, which is the first symptom of cytokine release syndrome, and ensuring that the syndrome was managed by appropriately trained site personnel using a protocol-specific algorithm, this serious toxic effect was controlled without fatal events.”
The JULIET investigators believe that “tisagenlecleucel has the potential to improve outcomes in patients with relapsed or refractory DLBCL”, but stress that “the potential for long-term toxic effects requires further analysis.”
Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med; Advance online publication 1 December 2018. doi: 10.1056/NEJMoa1804980
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