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.

Laetsch, T., Maude, S., Balduzzi, A., Rives, S., Bittencourt, H., Boyer, M., et al. (2022). Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia. LEUKEMIA, 36(6), 1508-1515 [10.1038/s41375-022-01550-z].

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

Balduzzi A.;
2022

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.
Articolo in rivista - Articolo scientifico
Adolescent; Antigens, CD19; Child; Child, Preschool; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cytokine Release Syndrome; Humans; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Remission Induction; Young Adult; Down Syndrome; Precursor Cell Lymphoblastic Leukemia-Lymphoma
English
1508
1515
8
Laetsch, T., Maude, S., Balduzzi, A., Rives, S., Bittencourt, H., Boyer, M., et al. (2022). Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia. LEUKEMIA, 36(6), 1508-1515 [10.1038/s41375-022-01550-z].
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
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/395695
Citazioni
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
Social impact