1. Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia
- Author
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Laetsch, T, Maude, S, Balduzzi, A, Rives, S, Bittencourt, H, Boyer, M, Buechner, J, De Moerloose, B, Qayed, M, Phillips, C, Pulsipher, M, Hiramatsu, H, Tiwari, R, Grupp, S, Laetsch T. W., Maude S. L., Balduzzi A., Rives S., Bittencourt H., Boyer M. W., Buechner J., De Moerloose B., Qayed M., Phillips C. L., Pulsipher M. A., Hiramatsu H., Tiwari R., Grupp S. A., Laetsch, T, Maude, S, Balduzzi, A, Rives, S, Bittencourt, H, Boyer, M, Buechner, J, De Moerloose, B, Qayed, M, Phillips, C, Pulsipher, M, Hiramatsu, H, Tiwari, R, Grupp, S, Laetsch T. W., Maude S. L., Balduzzi A., Rives S., Bittencourt H., Boyer M. W., Buechner J., De Moerloose B., Qayed M., Phillips C. L., Pulsipher M. A., Hiramatsu H., Tiwari R., and Grupp S. A.
- Abstract
Down syndrome-associated acute lymphoblastic leukemia (DS-ALL) patients suffer risk of chemotherapy-associated toxicities and poor outcomes. We evaluated tisagenlecleucel in 16 patients with DS-ALL in two phase 2 trials (ELIANA [NCT02435849], ENSIGN [NCT02228096]) and a phase 3b, managed access protocol (B2001X [NCT03123939]). Patients were 5–22 years old, had a median of two prior lines of therapy (range, 1–4), and four (25%) had prior stem cell transplants. Fourteen of 16 patients (88%) achieved complete remission (CR) or CR with incomplete blood count recovery (CRi); 12 of 14 (86%) with CR/CRi were minimal residual disease-negative. With a median follow-up of 13.2 months (range, 0.5–49.3 months), six patients (43%) relapsed after CR (three, CD19-negative; three, unknown) between 80–721 days post-infusion. Ongoing remissions in nine patients ranged from 6–48 months. Any-grade and grade 3/4 AEs occurred in 16 and 14 patients, respectively; 44% experienced grade 3/4 cytokine release syndrome and 13% experienced grade 3/4 neurological events. Grade 3/4 prolonged cytopenias occurred in 44% of patients. No grade 3/4 infections were observed. Tisagenlecleucel expansion and long-term persistence were consistent with previous reports. Comparable to ALL patients without DS, tisagenlecleucel produced high remission rates, manageable side-effects, and promising long-term outcomes in pediatric/young adult patients with DS-ALL.
- Published
- 2022