Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia.

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.

• Authors: Theodore W Laetsch, Shannon L Maude, Adriana Balduzzi, Susana Rives, Henrique Bittencourt, Michael W Boyer, Jochen Buechner, Barbara De Moerloose, Muna Qayed, Christine L Phillips, Michael A Pulsipher, Hidefumi Hiramatsu, Ranjan Tiwari, Stephan A Grupp
• Journal: Leukemia (Leukemia) Vol. 36 Issue 6 Pg. 1508-1515 (06 2022) ISSN: 1476-5551 [Electronic] England
• PMID: 35422096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Antigens, CD19
• Receptors, Antigen, T-Cell
• tisagenlecleucel

Topics

• Adolescent
• Antigens, CD19
• Child
• Child, Preschool
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Cytokine Release Syndrome
• Down Syndrome (complications)
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (complications, drug therapy)
• Receptors, Antigen, T-Cell
• Remission Induction
• Young Adult