MRD Assay Identifies Patients with ‘Very Low Risk’ of ALL Relapse

Early assessment of measurable residual disease (MRD) with a highly sensitive next-generation sequencing assay can identify patients with acute lymphoblastic leukemia (ALL) who have a “very low risk” of relapse and “excellent” long-term survival, according to a recent study.

Nicholas Short, MD, of the MD Anderson Cancer Center, and colleagues, conducted the research and published its results in Blood Advances.

Dr. Short and colleagues conducted the research because MRD is “highly prognostic” for relapse and overall survival (OS), but many patients with “apparent ‘MRD negativity’ by standard assays still relapse.”

They evaluated the clinical impact of using a highly sensitive next-generation sequencing MRD assay in 74 adults with ALL who were undergoing frontline therapy.  Among remission samples that were MRD negative by multiparameter flow cytometry, 46% were MRD positive when tested with the next-generation sequencing assay.

After a single cycle of induction chemotherapy, 66% of patients achieved MRD negativity by multiparameter flow cytometry at a sensitivity of 1 × 10⁻⁴, but only 23% of patients achieved MRD negativity by next-generation sequencing at a sensitivity of 1 × 10⁻⁶.

In patients who achieved MRD negativity by multiparameter flow cytometry testing at complete remission (CR), the five-year cumulative incidence of relapse was 29%. No relapses occurred in patients who achieved early MRD negativity per the next-generation sequencing assay, and their five-year OS rate was 90%.

Next-generation sequencing MRD negativity at CR was associated with a significantly decreased risk of relapse compared with next-generation sequencing MRD positivity at CR.

The five-year cumulative incidence of relapse was 0% in those with MRD negativity by next-generation sequencing at CR, while it was 45% in those with MRD positivity by next generation sequencing at CR (P=.04).

Of the patients who were MRD negative by multiparameter flow cytometry, “detection of low levels of MRD by [next-generation sequencing] identified patients who still had a significant risk of relapse,” according to Dr. Short and colleagues. The five-year cumulative incidence of relapse was 39% in those patients.

“Early assessment of MRD using a highly sensitive [next-generation sequencing] assay adds clinically relevant prognostic information to standard [multiparameter flow cytometry]-based approaches and can identify patients with ALL undergoing frontline therapy who have a very low risk of relapse and excellent long-term survival,” Dr. Short and colleagues concluded.

Reference

Short NJ, Kantarjian H, Ravandi F, et al. High-sensitivity next-generation sequencing MRD assessment in ALL identifies patients at very low risk of relapse. Blood Adv. 2022;6(13):4006-4014. doi:10.1182/bloodadvances.2022007378