As reported in the Journal of Clinical Oncology by Laetsch et al, the 3-year update of the phase II ELIANA trial showed durable responses and a manageable safety profile with tisagenlecleucel for the treatment of pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
The study supported the August 2017 U.S. Food and Drug Administration approval of tisagenlecleucel in this setting.
Study Details
In the international trial, 79 patients received tisagenlecleucel between April 2015 and July 2019. In the previously reported primary analysis—conducted in 75 patients, with a median follow-up of 13.1 months—the overall remission rate was 81%, with 59% of responders remaining relapse-free at 12 months.
Key Findings
Median follow-up for the updated analysis was 38.3 months. Remission was achieved in 65 (82%, 95% confidence interval [CI] = 72%–90%) of 79 patients within 3 months. Among the total of 66 patients in remission, the median duration of remission was not reached (95% CI = 17.8 months to not reached).
Median event-free survival was 24 months (95% CI = 9.2 months to not reached), with a 36-month rate of 44%. Median event-free survival among the 66 responders was not reached (95% CI = 18.7 months to not reached). Median overall survival was not reached (95% CI = not estimable to not estimable), with a 36-month rate of 63%.
Estimated relapse-free survival with censoring for allogeneic stem cell transplantation and/or further anticancer therapies was 58% at 24 months and 52% at 36 months. Estimated rates without censoring were 52% at 24 months and 48% at 36 months. Among 32 responders who received no subsequent therapy while in complete remission, the estimated rates were 81% at 24 months and 76% at 36 months.
No new or unexpected long-term adverse events were reported. Grade 3 or 4 adverse events occurred in 29% of patients at > 1 year after infusion, most commonly infections (20%) and skin disorders (6%). The incidence of grade 3 or 4 infections did not increase at > 1 year vs < 1 year after infusion.
Among 46 responding patients who completed the Pediatric Quality-of-Life Inventory and European Quality-of-Life-5 Dimensions questionnaire visual analog scale at baseline and at least one postbaseline visit, clinically meaningful improvements in health-related quality of life were observed as early as 3 months postinfusion, with continued improvements observed through 36 months.
The investigators concluded, “These findings demonstrate favorable long-term safety and suggest tisagenlecleucel as a curative treatment option for heavily pretreated pediatric and young adult patients with relapsed or refractory B-cell ALL.”
Theodore W. Laetsch, MD, of the Division of Oncology, The Children’s Hospital of Philadelphia, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Novartis Pharmaceuticals. For full disclosures of the study authors, visit ascopubs.org.
