ASH 2018: Updated Analysis of JULIET Trial: Tisagenlecleucel in Relapsed or Refractory DLBCL
In an update to the global JULIET clinical trial, the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah) led to long-lasting remissions in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The most recent results from the trial were presented by Schuster et al at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 1684). This updated analysis of the JULIET trial included a median of 19 months of follow-up.
Updated Findings
JULIET included 27 sites in 10 countries across North America, Europe, Australia, and Asia. According to the data presented, 115 patients with relapsed or refractory DLBCL received an infusion of CAR T cells. The overall response rate of evaluable patients was 54% (95% confidence interval [CI] = 43%–64%), with 40% achieving a complete response and 13% achieving a partial response. The median duration of those responses was not reached at a median follow-up of 19 months.
The probability of being relapse-free was 66% (95% CI = 51%–78%) at 6 months and 64% (95% CI = 48%–76%) at 12 and 18 months. No relapses were observed beyond 11 months after infusion. The median overall survival for all infused patients was 11.1 months (95% CI = 6.6 months–not evaluable) and not reached (95% CI = 21 months–not evaluable) for patients in complete response. No patients proceeded to allogeneic or autologous stem cell transplant while in remission.
Grade 3/4 cytokine-release syndrome was reported in 23% of patients, 16% of whom required treatment with tocilizumab, which is the standard therapy for the toxicity; all patients recovered. Other grade 3 or 4 toxicities included infections (19%), febrile neutropenia (15%), neurologic events (11%), and tumor-lysis syndrome (2%). Three patients died within 30 days of infusion, all due to disease progression, but there were no treatment-related deaths.
“These findings are consistent with what we've shown in our single-site studies … which is that the majority of patients who go into remission stay in remission,” said senior author Stephen J. Schuster, MD, of the Perelman School of Medicine at the University of Pennsylvania, in a statement. “CAR T therapy represents a potentially life-saving alternative for these patients, who now have a therapy that can help them achieve durable remissions even after other therapies, including transplant, have failed,” he concluded.
In May 2018, tisagenlecleucel was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refactory large B-cell lymphoma after two or more lines of systemic therapy, including DLCBL, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The original FDA approval of the agent came in August 2017 for the treatment of patients up to 25 years of age with acute lymphoblastic leukemia that is refractory or in second or later relapse.
Disclosure: See the study authors’ full disclosures at ash.confex.com.
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