MRD Testing a Crucial Component in Treatment of Patients With AML

New York—Clinicians should be measuring minimal residual disease (MRD) in their patients with acute myeloid leukemia (AML), because complete remission (CR) on its own is simply not enough, according to a presentation given at the 2018 Lymphoma & Myeloma congress.

Enhancing Complete Relapse Data With MRD

Speaking to attendees, Gail J. Roboz, MD, Professor of Medicine and Director, Clinical and Translational Leukemia Programs, Weill Cornell Medicine, NewYork-Presbyterian Hospital, discussed what MRD is, and how it should be addressed.

“CR alone isn’t good enough; you want more than that,” Dr Roboz said of MRD when referencing the burgeoning term for MRD-negative CR (ie, CR_MRD−) being used more often in literature.

Approximation of disease burden reduction can be gleaned through quantification of MRD, which reflects factors including mechanisms of drug-resistance, therapy adequacy, and patient–drug interactions that could affect treatment response.

Methods for measuring MRD include cytogenetics, flow cytometry, real-time quantitative polymerase chain reaction, and next-generation sequencing.

MRD Detection and Risk for Disease Relapse

In a recent study (N Engl J Med. 2018;378:1189–119), 482 patients with newly diagnosed AML underwent targeted next-generation sequencing and multiparameter flow cytometry at diagnosis and postinduction, resulting in the detection of at least 1 mutation in 430 (89.2%) patients. The mutations persisted in >50% of patients who had complete remission at various allele frequencies.

According to Dr Roboz, these results demonstrated a correlation between detection of molecular MRD after AML induction and increased relapse rates and death.

“Having persistent mutations did not correlate with good outcomes. You can see here that if you have detectable mutations by sequencing in combination with detectable mutations by flow cytometry your chances of relapse are enormous,” she said.

Another study that Dr Roboz highlighted included 194 patients with newly diagnosed AML (median age, 76 years) receiving treatment with azacitidine, decitabine, or guadecitabine. A total of 116 of these patients underwent MRD analysis with flow cytometry.

Results showed that there were evaluable MRD data for 61 (53%) patients. CR, CR with incomplete platelet recovery, and CR with incomplete hematologic recovery were achieved in 69 (59%) patients.

Achievement of a negative MRD state after therapy with a hypomethylating drug reduced the risk for relapse in older patients with AML, Dr Roboz explained.

MRD in Transplant Recipients and as a Standard of Care

In transplant recipients, MRD should be assessed pre- and post-transplant; however, Dr Roboz noted, as of yet it is undetermined whether this should be done with flow cytometry or next-generation sequencing.

“It really is MRD that is driving these transplant related outcomes,” she said.

“We want to use MRD to get a better perception of how our patients are going to do. Monitoring of MRD should be included in standard of care,” Dr Roboz told listeners.—Hina Khaliq