Next-Generation Sequencing of Minimal Residual Disease for Predicting Relapse after Tisagenlecleucel in Children and Young Adults with Acute Lymphoblastic Leukemia

Autor: Gabor Kari, André Baruchel, Hidefumi Hiramatsu, Peter Bader, Timothy A. Driscoll, Jochen Buechner, Muna Qayed, Kevin Nguyen, Xia Han, Shannon L. Maude, G. Doug Myers, Michael A. Pulsipher, Gregory A. Yanik, Stephan A. Grupp, Edward Waldron, Creton Kalfoglou, Karen Thudium Mueller, Susana Rives, Theodore W. Laetsch, Harald J. Maier, Michael Boyer, Heather E. Stefanski
Rok vydání: 2021
Předmět:
Zdroj: Blood Cancer Discovery. 3:66-81
ISSN: 2643-3249
2643-3230
Popis: 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− (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
Databáze: OpenAIRE
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