Back to Search
Start Over
Next-Generation Sequencing of Minimal Residual Disease for Predicting Relapse after Tisagenlecleucel in Children and Young Adults with Acute Lymphoblastic Leukemia.
- Source :
-
Blood cancer discovery [Blood Cancer Discov] 2022 Jan; Vol. 3 (1), pp. 66-81. Date of Electronic Publication: 2021 Dec 01. - Publication Year :
- 2022
-
Abstract
- We assessed minimal residual disease (MRD) detection and B-cell aplasia after tisagenlecleucel therapy for acute lymphoblastic leukemia (ALL) to define biomarkers predictive of relapse ( N = 143). Next-generation sequencing (NGS) MRD detection >0 in bone marrow (BM) was highly associated with relapse. B-cell recovery [signifying loss of functional chimeric antigen receptor (CAR) T cells] within the first year of treatment was associated with a hazard ratio (HR) for relapse of 4.5 [95% confidence interval (CI), 2.03-9.97; P < 0.001]. Multivariate analysis at day 28 showed independent associations of BMNGS-MRD >0 (HR = 4.87; 95% CI, 2.18-10.8; P < 0.001) and B-cell recovery (HR = 3.33; 95% CI, 1.44-7.69; P = 0.005) with relapse. By 3 months, the BMNGS-MRD HR increased to 12 (95% CI, 2.87-50; P < 0.001), whereas B-cell recovery was not independently predictive (HR = 1.27; 95% CI, 0.33-4.79; P = 0.7). Relapses occurring with persistence of B-cell aplasia were largely CD19 <superscript>-</superscript> (23/25: 88%). Detectable BMNGS-MRD reliably predicts risk with sufficient time to consider approaches to relapse prevention such as hematopoietic cell transplantation (HCT) or second CAR-T cell infusion. SIGNIFICANCE: Detectable disease by BMNGS-MRD with or without B-cell aplasia is highly predictive of relapse after tisagenlecleucel therapy for ALL. Clonotypic rearrangements used to follow NGS-MRD did not change after loss of CD19 or lineage switch. High-risk patients identified by these biomarkers may benefit from HCT or investigational cell therapies. See related commentary by Ghorashian and Bartram, p. 2 . This article is highlighted in the In This Issue feature, p. 1 .<br /> (©2021 The Authors; Published by the American Association for Cancer Research.)
Details
- Language :
- English
- ISSN :
- 2643-3249
- Volume :
- 3
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Blood cancer discovery
- Publication Type :
- Academic Journal
- Accession number :
- 35019853
- Full Text :
- https://doi.org/10.1158/2643-3230.BCD-21-0095