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

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.

Graphical abstract

Figure 1.

CONSORT diagram. 1, patients without the complete set of baseline forms were excluded; 2, infusion set is the cohort with complete baseline information at the time of data freeze; 3, identifiable tisagenlecleucel batch numbers with available product characteristics; 4, analysis set defined as patients with available follow-up forms after tisagenlecleucel with information related to safety and efficacy outcomes.

Figure 2.

Safety outcomes among patients treated with tisagenlecleucel. CRS (A-B) and ICANS (C-D) by disease: ALL (A,C) and NHL (B,D).

Figure 3.

Efficacy outcomes for recipients of tisagenlecleucel. DOR (A), EFS (B) and OS (C) in patients with ALL, and DOR (D), PFS (E), and OS (F) in patients with NHL. CRi, CR with incomplete hematologic recovery; NE, not evaluable.

Figure 4.

Correlation of cell product release specifications with clinical outcome. Logistic regression of BOR (A,C,E) and CRS (B,D,F) vs dose for ALL ≤50 kg (A-B), ALL >50 kg (C-D), and NHL (E-F).