MRD Status Indicated Therapeutic Benefit in Pediatric, Adult ALL

There is considerable value in having achieved a minimal residual disease negativity for pediatric and adult patients with acute lymphoblastic leukemia.

There is considerable value in having achieved a minimal residual disease (MRD) negativity for pediatric and adult patients with acute lymphoblastic leukemia (ALL), according to the results of a meta-analysis published recently in JAMA Oncology.

The analysis, which included data from 39 publications and more than 13,500 patients showed the value of MRD negativity across therapies used, methods of and times of MRD assessment, cutoff levels, and disease subtypes.

“Minimal residual disease status in patients with ALL is an indicator of therapeutic benefit in clinical practice,” wrote researcher Donald A. Berry, PhD, of the department of biostatistics at The University of Texas MD Anderson Cancer Center in Houston, and colleagues. “It has great potential for making drug development more efficient by providing early evidence of treatment benefit.”

Presence of MRD has been associated with higher relapse rates across a variety of hematologic malignancies. Studies of ALL have shown that MRD was associated with poorer event-free (EFS) and overall survival (OS). However, “using MRD assessment to guide clinical treatment may depend on the strength of association, its robustness across studies, its dependence on disease subtype and the patient’s clinical and demographic characteristics,” wrote Berry and colleagues.

Therefore, they conducted this meta-analysis to address the extent to which MRD negativity was associated with better long-term clinical outcomes. The review included clinical studies in ALL that addressed EFS and OS by MRD status in patients with ALL. They included 39 publications with 13,637 patients: 16 adult studies, 20 pediatric studies, and 3 mixed populations.

“Our study confirms MRD as a measure of disease burden that is an early response indicator for use in the design and conduct of clinical trials,” the researchers wrote. “As such, achieving MRD negativity may qualify as an end point for drug registration.”

According to the meta-analysis, the EFS hazard ratio (HR) for achieving MRD negativity was 0.23 for pediatric patients and 0.28 for adults. The estimated EFS in the pediatric population was 77% at 10 years with MRD negativity compared with 32% with MRD positivity. Among adults the estimated EFS with MRD negativity was 64% at 10 years compared with 21% for those who were MRD positive.

The HR was overall survival was 0.28 for pediatric patients and 0.28 for adult patients.

“Minimal residual disease negativity leads to better clinical outcomes in the studies we considered. But this same relationship may not apply for therapies we did not consider,” the researchers wrote. “A new therapy might decrease the rate of MRD but not affect clinical outcome. Or it might have no effect on rate of MRD but still improve outcome. Using MRD as a primary end point for accelerated approval of a new drug will require a plan for confirming benefit on EFS or OS.”