Two studies are suggesting more tailored approaches to better discriminate true minimal/measurable residual disease (MRD) positivity for risk stratification in chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) in children. Researchers from both studies are suggesting a change in the standard of care when using MRD positivity for risk stratification.

In a study with 67 patients published in Blood, researchers found that a next-generation sequencing (NGS) assay could routinely detect and quantify MRD to 10−5 and beyond in CLL.1 The investigators used their academically-developed immunoglobulin heavy-chain variable (IGHV) leader-based NGS assay and found it could improve the prognostic stratification in CLL in MRD quantification below 10−4.

The authors noted that the sensitivity of conventional techniques for reliable quantification of MRD in CLL currently is limited to MRD10−4. However, measuring MRD <10−4 may help to better distinguish between patients with CLL who are in durable remission from those who are at risk of early relapse.

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The investigators used MRD 10−5 as a cutoff and undetectable MRD was associated with superior progression-free survival (PFS) and time to next treatment. They found that a deeper MRD measurement allowed for additional stratification of patients with MRD <10−4 but ≥10−5.

The study demonstrated that PFS of patients in the MRD 10−4 range was significantly shorter, compared with patients with MRD <10−5 (hazard ratio [HR], 4.0; 95% CI, 1.6-10.3; P =.004). However, it was significantly longer when the researchers compared patients with MRD ≥10−4 (HR, 0.44; 95% CI, 0.23-0.87; P =.018). The authors concluded that these results support the clinical utility of the IGHV leader-based NGS assay. 

In a separate study published in Blood, researchers found that frontline NGS MRD evaluation can be used as an alternative to traditional qPCR-based MRD quantitation in future MRD-based treatment protocols in pediatric patients with ALL.2

A large cohort of pediatric patients with ALL were treated between 2009 and 2018 on the AIEOP-BFM ALL 2009 protocol diagnosed with B-cell precursor ALL in the Czech Republic. The researchers found that NGS MRD evaluation could be “immediately implemented in off-protocol treatment monitoring and independent evaluation” of positive non quantifiable (PnQ) results of quantitative PCR (qPCR), typically after stem cell transplant.

Study investigator Eva Frankova, with the CLIP-Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, Charles University and University Hospital Motol, Prague, Czech Republic, said MRD in ALL is one of the most important tools for stratifying patients into therapeutic risk groups. However, the most sensitive method used in pediatric ALL treatment protocols has been qPCR.