Tisagenlecleucel for the Treatment of Pediatric and Young Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia: Updated Analysis of the ELIANA Clinical Trial

BKGD The ELIANA study of tisagenlecleucel in pediatric and young adult patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) demonstrated an overall remission rate (ORR) of 81% and led to FDA approval. We report an updated analysis with additional pts and longer follow-up. MTD Enrolment criteria included age ≥3 y at screening and ≤21 y at diagnosis, and ≥5% leukemic blasts in bone marrow. Tisagenlecleucel was manufactured at 2 sites (Morris Plains, NJ, USA; Leipzig, Germany) by autologous T-cell transduction with a lentiviral vector encoding a 2nd-generation 4-1BB anti-CD19 CAR and expanded ex vivo. The primary endpoint was ORR within 3 mo and maintained ≥28 d. Secondary endpoints included duration of remission (DOR), overall survival (OS), safety, and cellular kinetics. RTS As of 13 April 2018, 113 pts were screened and 97 enrolled. A single tisagenlecleucel infusion (median dose, 3.0 × 10 6 [range, 0.2-5.4 × 10 6 ] CAR(+) viable T cells/kg) was given to 79 pts, followed for ≥3 mo (median time from infusion to data cutoff = 24 mo [range, 4.5-35 mo]). Median age = 11 y (range, 3-24 y). Infusions were not given in 18 pts due to death or adverse events (AEs), n=10; or manufacturing failures, n=8. Among infused pts, 61% had a prior hematopoietic stem cell transplant (SCT). CR/CRi was achieved by 65 pts (Table); 64 (98%) were MRD(–) ≤3 mo. Median DOR not reached; 29 pts had ongoing responses (max DOR was 29 mo and ongoing; Figure). Median OS not reached; OS probability at 18 mo was 70% (95% CI, 58%-79%). Nineteen pts relapsed before additional anticancer therapy (13 pts died thereafter). Eight pts in remission had SCT, 8 had additional anticancer therapy (non-SCT), and 1 discontinued the study. Relapse-free survival (RFS) at 18 mo was 66% (95% CI, 52%-77%). Cytokine release syndrome (CRS) was seen in 77% of pts (48% grade 3/4; Penn scale); all were reversible. Other common (>15%) grade 3/4 nonhematologic AEs were neutropenia with a body temperature >38.3°C (62% ≤8 wk of infusion), hypoxia (20%), and hypotension (20%). Grade 3 neurologic events were seen in 13% of pts. Twenty-five postinfusion deaths occurred (2 ≤30 d postinfusion; 23 >30 d). Tisagenlecleucel expansion in vivo correlated with CRS severity. Tisagenlecleucel persistence and B-cell aplasia in peripheral blood were observed for ≥2.5 y in some responding pts. Correlation of B-cell recovery and relapse will be presented. CONS Longer follow-up demonstrated continued efficacy and safety of tisagenlecleucel in pediatric and young adult pts with ALL. Patients continued to achieve high ORR, deep and durable remissions, and high OS. AEs continued to be effectively managed.