Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma

TLDR

Tisagenlecleucel is a CD19‑targeted CAR T‑cell therapy approved for relapsed or refractory pediatric and young adult acute lymphoblastic leukemia and for adult non‑Hodgkin lymphoma. The study reports the first real‑world experience with tisagenlecleucel using data from a cellular therapy registry. As of January 2020, 511 patients from 73 centers were enrolled, with 410 having follow‑up data (255 ALL, 155 NHL) and median follow‑up of 13.4 months for ALL and 11.9 months for NHL. In this cohort, 85.5 % of ALL patients achieved complete remission and 12‑month DOR, EFS, and OS were 60.9 %, 52.4 %, and 77.2 %; for NHL, 61.8 % achieved overall response (39.5 % CR) with 6‑month DOR, PFS, and OS of 55.3 %, 38.7 %, and 70.7 %; grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 11.6 % and 7.5 % of patients, and outcomes were comparable between in‑spec and out‑of‑spec products, demonstrating efficacy similar to pivotal trials but with improved safety.

Abstract

Abstract Tisagenlecleucel is a CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and adults with non-Hodgkin lymphoma (NHL). The initial experience with tisagenlecleucel in a real-world setting from a cellular therapy registry is presented here. As of January 2020, 511 patients were enrolled from 73 centers, and 410 patients had follow-up data reported (ALL, n = 255; NHL, n = 155), with a median follow-up of 13.4 and 11.9 months for ALL and NHL, respectively. Among patients with ALL, the initial complete remission (CR) rate was 85.5%. Twelve-month duration of response (DOR), event-free survival, and overall survival (OS) rates were 60.9%, 52.4%, and 77.2%, respectively. Among adults with NHL, the best overall response rate was 61.8%, including an initial CR rate of 39.5%. Six-month DOR, progression-free survival, and OS rates were 55.3%, 38.7%, and 70.7%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 11.6% and 7.5% of all patients, respectively. Similar outcomes were observed in patients with in-specification and out-of-specification products as a result of viability <80% (range, 61% to 79%). This first report of tisagenlecleucel in the real-world setting demonstrates outcomes with similar efficacy and improved safety compared with those seen in the pivotal trials.