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Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia.
- Source :
-
Leukemia [Leukemia] 2021 Dec; Vol. 35 (12), pp. 3383-3393. Date of Electronic Publication: 2021 May 17. - Publication Year :
- 2021
-
Abstract
- Tisagenlecleucel therapy has shown promising efficacy for relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, relapses occur in 30-50% of patients. Determinants for CD19 <superscript>pos</superscript> versus CD19 <superscript>neg</superscript> relapses are poorly characterized. We report on 51 patients with R/R BCP-ALL (median age 17 years) infused with tisagenlecleucel after lymphodepletion. Complete remission rate at D28 was 96%. Prior blinatumomab increased the risk of early failure at D28. The 18-month cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 51%, 44%, and 74%, respectively, at a median follow-up of 15.5 months. Factors associated with a high tumor burden (occurrence of cytokine release syndrome) and prior blinatumomab were associated with an increased CIR, and a shorter EFS and OS. Pre-lymphodepletion high disease burden (MRD ≥ 10 <superscript>-2</superscript> , SHR 10.4, p = 0.03) and detectable MRD at D28 (SHR 7.2, p = 0.006) correlated with an increased risk of CD19 <superscript>neg</superscript> relapse. Low disease burden (SHR 5.3, p = 0.03) and loss of B-cell aplasia (BCA) (SHR 21.7, p = 0.004) predicted an increased risk of CD19 <superscript>pos</superscript> relapses. These data highlight the impact of prior therapy on patient outcome. Finally, detectable MRD at D28 and loss of BCA both define patients at high risk of relapse for whom additional interventions are needed.<br /> (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- Adolescent
Adult
B-Lymphocytes drug effects
Child
Child, Preschool
Female
Follow-Up Studies
Humans
Infant
Male
Neoplasm Recurrence, Local pathology
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology
Prognosis
Prospective Studies
Survival Rate
Young Adult
Antigens, CD19 metabolism
Antineoplastic Agents, Immunological therapeutic use
B-Lymphocytes pathology
Neoplasm Recurrence, Local drug therapy
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy
Receptors, Antigen, T-Cell therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5551
- Volume :
- 35
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 34002027
- Full Text :
- https://doi.org/10.1038/s41375-021-01281-7