Tisagenlecleucel shows high rates of durable responses in adults with relapsed/refractory DLBCL
The anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel has demonstrated high rates of durable responses in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in the pivotal international JULIET study.
The phase II, open-label, single-group study was conducted at 27 sites in 10 countries across North America, Europe, Australia and Asia. Among 93 patients (median age, 56 years) who received an infusion of centrally manufactured tisagenlecleucel and had ≥3 months of follow-up or discontinued study participation before 3 months, the primary endpoint of best overall response rate (ie, percentage of patients with a complete response [CR] or partial response [PR]) was 52 percent (95 percent confidence interval [CI], 41 to 62), with 40 percent of patients achieving a CR and 12 percent achieving a PR. [N Engl J Med 2019;380:45-56]
Of note, 16 of the 37 complete responders initially had stable disease (n=4) or PR (n=12) at 1 month after infusion, which improved to CR in a median of 2 months. Thirteen of 24 patients converted from PR to CR.
Rates of overall and complete response at 3 months were 38 percent and 32 percent, respectively, and were 33 percent and 29 percent at 6 months. “This suggests that responses at 3 months are usually durable,” the investigators commented.
According to the investigators, there were no substantial differences in response rates according to the type of lymphodepleting therapy received or between demographic and prognostic subgroups.
“Thirty-five patients were in remission at 3 months. The estimated probability of remaining in remission at 12 months was 81 percent [95 percent CI, 63 to 91],” the investigators reported.
The median duration of response was not reached (95 percent CI, 10 months to not reached), with 79 percent of complete responders and 65 percent of all responders projected to remain relapse-free at 12 months after achieving a response. “Durable responses were observed for up to 18.4 months after infusion,” the investigators added.
Median progression-free survival (PFS) was not reached among complete responders. The estimated 12-month PFS rate was 83 percent among patients who achieved CR or PR at 3 months.
Median overall survival (OS) was 12 months among patients who received an infusion, with an estimated 12-month OS rate of 49 percent among all patients and 90 percent among complete responders.
In terms of safety, the most common grade 3/4 adverse events of special interest included cytokine release syndrome (22 percent), neurologic events (12 percent), cytopenia lasting >28 days (32 percent), infections (20 percent), and febrile neutropenia (14 percent). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral oedema.
In the study, 95 percent of the 111 patients who received an infusion of tisagenlecleucel had previously received ≥2 lines of antineoplastic therapy. Before tisagenlecleucel infusion, 92 percent of the patients received bridging therapy, including combinations of rituximab (54 percent), gemcitabine (40 percent), etoposide (26 percent), dexamethasone (25 percent), cisplatin (19 percent) and cytarabine (19 percent), as well as ibrutinib (9 percent) and lenalidomide (7 percent).Although the high rates of durable responses observed in the study are promising, the investigators pointed out that follow-up was short, and the potential for long-term toxicity required further analysis.