Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In the primary analysis of the global phase II ELIANA trial (ClinicalTrials.gov identifier: NCT02435849), tisagenlecleucel provided an overall remission rate of 81% in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), with 59% of responders remaining relapse-free at 12 months. Here, we report an update on efficacy, safety, and patient-reported quality of life in 79 pediatric and young adult patients with R/R B-ALL following a median follow-up of 38.8 months. The overall remission rate was 82%. The median event-free survival was 24 months, and the median overall survival was not reached. Event-free survival was 44% (95% CI, 31 to 57) and overall survival was 63% (95% CI, 51 to 73) at 3 years overall (most events occur within the first 2 years). The estimated 3-year relapse-free survival with and without censoring for subsequent therapy was 52% (95% CI, 37 to 66) and 48% (95% CI, 34 to 60), respectively. No new or unexpected long-term adverse events were reported. Grade 3/4 adverse events were reported in 29% of patients > 1 year after infusion; grade 3/4 infection rate did not increase > 1 year after infusion. Patients reported improvements in quality of life up to 36 months after infusion. These findings demonstrate favorable long-term safety and suggest tisagenlecleucel as a curative treatment option for heavily pretreated pediatric and young adult patients with R/R B-ALL.

FIG 1.

(A) DOR, (B) EFS, and (C) OS. (A) DOR—patients who achieved a BOR of CR/CRi are included. One patient who achieved a BOR of CRi within 6 months (day 173) is included. Time is relative to detection of remission. (B) EFS—time is relative to first tisagenlecleucel infusion date. (C) OS—time is relative to first tisagenlecleucel infusion date. BOR, best overall response; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; DOR, duration of remission; EFS, event-free survival; NE, not estimable; OS, overall survival.

FIG 2.

Duration of remission by B-cell recovery time point. Time is relative to first tisagenlecleucel infusion date. EFS, event-free survival; NE, not estimable.