微小残留病二代测序预测儿童与年轻成人急性淋巴细胞白血病患者 Tisagenlecleucel 治疗后的复发

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 .