Minimal residual disease negativity linked to improved outcome in ALL
medwireNews: Patients with acute lymphoblastic leukemia (ALL) and no minimal residual disease (MRD) are much more likely to be alive and disease-free at 10 years than those with measurable disease following therapeutic intervention, meta-analysis data show.
This suggests that “MRD status is a useful indicator of therapeutic benefit in clinical practice and has potential for making drug development more efficient by providing early evidence of treatment benefit,” Donald Berry (The University of Texas MD Anderson Cancer Center, Houston, USA) and co-authors remark.
Berry and team reviewed data for 13,637 adult and pediatric patients participating in 39 studies.
They found that 10-year event-free survival (EFS) was 77% in pediatric patients with no MRD versus 32% in those with MRD. The corresponding values in adults were 64% and 21%.
This translates to hazard ratios of 0.23 for pediatric patients and 0.28 for adults, indicating that the risk for recurrence with MRD is reduced by a significant 77% and 72%, respectively, by achieving MRD negativity.
Similar results were observed for overall survival (OS) with 84% of MRD-negative pediatric patients and 60% of MRD-negative adult patients alive at 10 years, compared with 55% and 15%, respectively, of MRD-positive patients. The resulting hazard ratios for overall survival were 0.28 in both groups.
The researchers note that the beneficial effect of achieving MRD negativity was consistent across all studies and subgroups they analyzed, including disease subtypes, therapy type, MRD assessment type, and MRD cut-off.
“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. As such, achieving MRD negativity may qualify as an end point for drug registration,” Berry el al write in JAMA Oncology.
However, the researchers caution that MRD negativity may not be associated with improved outcome for therapies they did not consider.
“A new therapy might decrease the rate of MRD but not affect clinical outcome. Or it might have no effect on [the] rate of MRD but still improve outcome,” they say.
Therefore “[u]sing MRD as a primary end point for accelerated approval of a new drug will require a plan for confirming benefit on EFS or OS,” Berry and team conclude.
By Laura Cowen
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