Researchers say they have identified a reliable predictor of relapse after chimeric antigen receptor (CAR) T-cell therapy in patients with CD19-positive, relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

Minimal residual disease (MRD) in the bone marrow, detected via next-generation sequencing (NGS), was “highly predictive” of relapse after treatment with tisagenlecleucel, the researchers wrote in Blood Cancer Discovery.

For this study, the researchers analyzed blood and bone marrow samples from pediatric and young adult patients in the phase 2 ELIANA (ClinicalTrials.gov Identifier: NCT02435849) and ENSIGN (ClinicalTrials.gov Identifier: NCT02228096) trials.


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The researchers compared NGS MRD detection with MRD detection via multiparameter flow cytometry (MFC). They also investigated the utility of B-cell aplasia as a potential biomarker for relapse.

The researchers analyzed 1771 MFC samples from 143 patients and 474 NGS samples from 109 patients. Both MFC and NGS detected a higher percentage of blasts in bone marrow than in peripheral blood.

Bone marrow NGS-MRD resulted in comparable detection to bone marrow MFC-MRD at levels above 10-4, but NGS-MRD “was much more sensitive,” according to the researchers.

They also found that bone marrow NGS-MRD greater than 0 and B-cell recovery were both associated with the risk of relapse.

In multivariate analyses, bone marrow NGS-MRD greater than 0 was independently associated with relapse at day 28 (hazard ratio [HR], 4.87; 95% CI, 2.18–10.8; P <.001) and at 3 months (HR, 12.0; 95% CI, 2.87–50; P <.001).

B-cell recovery was independently associated with relapse at day 28 (HR, 3.33; 95% CI, 1.44–7.69; P =.005) but not at 3 months (HR, 1.27; 95% CI, 0.33–4.79; P =.7).

“This study demonstrates that the best biomarker described to date for determining risk of relapse at any given time throughout the first year after CAR T-cell therapy with tisagenlecleucel is NGS-MRD assessment of the marrow with a cutoff of >0 cells detected,” the researchers wrote. “B-cell aplasia during the first year is also a strong biomarker, defining patients with possible long-term response.”

Disclosures: The ELIANA and ENSIGN trials were sponsored by Novartis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference                                                   

Pulsipher MA, Han X, Maude SL, et al. Next-generation sequencing of minimal residual disease for predicting relapse after tisagenlecleucel in children and young adults with acute lymphoblastic leukemia. Published online December 1, 2021. Blood Cancer Discov. doi:10.1158/2643-3230.BCD-21-0095