‘Ultrasensitive’ MRD Assessment Is Prognostic in Ph+ ALL

A next-generation sequencing (NGS)-based assessment of measurable residual disease (MRD) identified patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who were “unlikely to relapse nor to benefit from therapeutic interventions,” according to a recent study.

Nicholas Short, MD, and Elias Jabbour, MD, both of the MD Anderson Cancer Center, and colleagues conducted the research and published their findings in the American Journal of Hematology.

While reverse-transcription polymerase chain reaction (RT-PCR) testing for BCR::ABL1 is the “most common and widely accepted method” of MRD assessment in Ph+ ALL, it “may not be an optimal measure of MRD in many cases,” the study’s authors wrote.

Due to this, they evaluated an NGS assay with a sensitivity level of 10⁻⁶ for MRD and its correlation with RT-PCR assay results for BCR::ABL1 in patients with Ph+ ALL.

The RT-PCR and NGS assessments showed discordant results in samples from 32% of patients. Nearly one-third (31%) of patients had positive results on the RT-PCR assay and MRD-negative results on the NGS assay at the same time point. Among the eight patients who had long-term detectable BCR::ABL1 on the RT-PCR assay, six had MRD-negative results on the NGS assay.

“These patients generally had stable PCR levels that persisted despite therapeutic interventions, and none subsequently relapsed; in contrast, patients who were [positive on both PCR and NGS] had more variable PCR values that responded to therapeutic intervention,” the study’s authors wrote.

When the researchers prospectively collected clinical samples from a separate cohort of 65 patients, 11 (17%) of those patients had MRD-negative results on the NGS assay, but had detectable BCR::ABL1 results on the RT-PCR assay. However, none of those patients relapsed.

Relapse-free survival and overall survival were “similar” in patients with a positive result on RT-PCR and a negative result on NGS, and in those with negative results on both RT-PCR and NGS, “suggesting that PCR for BCR::ABL1 did not provide additional prognostic information in patients who achieved NGS MRD negativity,” according to the researchers.

They concluded that the NGS-based assessment of MRD is “prognostic in Ph+ ALL and identifies patients with low-level detectable BCR::ABL1 who are unlikely to relapse nor to benefit from therapeutic interventions.”

Reference

Short NJ, Jabbour E, Macaron W, et al. Ultrasensitive NGS MRD assessment in Ph+ ALL: prognostic impact and correlation with RT-PCR for BCR::ABL1. Am J Hematol. 2023. doi:10.1002/ajh.26949