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NGS comparable to FC for minimal residual disease assessment



– Next-generation sequencing of peripheral blood is at least as effective as flow cytometry of bone marrow for assessing minimal residual disease, according to a new study.

Researchers compared bone marrow flow cytometry (FC) and peripheral blood next-generation sequencing (NGS) for minimal residual disease (MRD) assessment in pediatric and young adult patients with B-cell acute lymphoblastic leukemia (B-ALL) who received treatment with tisagenlecleucel. There was a high level of concordance between the assays, but the NGS assay detected more MRD-positive samples and NGS results provided a longer lead time to relapse.

Michael A. Pulsipher, MD, of the Children’s Hospital Los Angeles, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The researchers analyzed samples from pediatric and young adult patients aged 2-25 years who had relapsed or refractory B-ALL and received treatment with tisagenlecleucel on the ELIANA or ENSIGN trials.

The patients had received at least two prior lines of therapy and were ineligible for allogeneic transplant. They received a single dose of tisagenlecleucel. MRD was assessed before tisagenlecleucel infusion, at various time points after infusion, and at relapse.

Dr. Pulsipher and his colleagues compared MRD results from an NGS assay – Adaptive Biotechnologies’ clonoSEQ – using peripheral blood and results from FC of bone marrow. NGS and FC results were available for 237 samples from 83 patients.

After treatment, NGS detected more MRD-positive samples at each sensitivity level tested (10-4, 10-5, and 10-6). At 10-6, NGS detected 18% more MRD-positive samples than did FC – 50% and 32%, respectively.

Detection of MRD positivity prior to relapse was faster with NGS than with FC. In 17 of 34 patients with morphological relapse, NGS provided a median lead time of 67 days. FC provided a median lead time of 39 days in 11 of the 34 patients.

About 80% of patients who had an MRD status of zero by NGS at day 28 remained relapse-free for up to 3 years.

Among complete responders (n = 50), the duration of response was significantly longer in patients who had an MRD status of zero at day 28 by NGS than in patients who had an MRD status greater than zero (P = .0003). Overall survival was significantly better among patients with an MRD status of zero as well (P = .0004).

Dr. Pulsipher said additional studies are needed to confirm these findings and determine the best way to know if a patient has been cured or needs additional therapy after tisagenlecleucel.

Dr. Pulsipher reported relationships with Adaptive Biotech, Novartis, Incyte, Amgen, Bellicum Pharmaceuticals, Medac Pharma, and Miltenyi Biotec. ELIANA and ENSIGN were funded by Novartis, which markets tisagenlecleucel as Kymriah.

SOURCE: Pulsipher MA et al. ASPHO 2019, Abstract 2001.

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