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Minimal residual disease after induction predicts transplant benefit in NPM1–mutated AML
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Postinduction minimal residual disease predicted benefit of allogeneic stem cell transplantation among patients with NPM1–mutated acute myeloid leukemia, according to results of a study conducted in France.
“In patients with acute lymphoblastic leukemia or chronic myeloid leukemia, minimal residual disease (MRD) levels routinely guide treatment decisions at different checkpoints. Several groups have shown a good correlation between early [NPM1m–positive MRD] level and patient outcome,” Marie Balsat, MD, of Centre Hospitalier Lyon Sud in Pierre Benite, France, and colleagues wrote. “In these studies, absolute quantifications of NPM1m MRD either in peripheral blood or bone marrow at different time points were strong prognostic factors for subsequent outcome. However, the consequences in terms of therapeutic decisions remain to be investigated.”
Balsat and colleagues obtained MRD data from 152 patients (age range, 18-60 years) in first remission who had been treated in the Acute Leukemia French Association 0702 trial between April 2009 and August 2013.
Median follow-up was 3.48 years (95% CI, 3.08-3.92).
All but three patients in the study achieved either complete remission or remission with incomplete platelet recovery after one round of induction therapy.
The researchers reported a higher cumulative incidence of relapse among patients who did not experience a 4-log reduction in NPM1m–peripheral blood MRD (subhazard ratio: 5.83; P < .001). These patients also exhibited shorter OS (HR = 10.99; P < .001).
Multivariable analysis indicated that FLT3–internal tandem duplication, abnormal karyotype, and a reduction of less than 4-log in peripheral blood MRD all were associated with higher incidences of relapse and shorter OS.
Among individuals with FLT3-internal tandem duplication, multivariable analysis showed three factors — age, white blood cell count, and less than 4-log reduction of peripheral blood MRD — were of “significant prognostic value,” researchers wrote.
Patients who did not achieve 4-log reduction in NPM1m–peripheral blood MRD had a better response to stem cell transplantation than those who achieved a greater than 4-log reduction.
There was “significant reaction” between peripheral blood MRD response and efficacy of stem cell transplantation (DFS, P = .024; OS, P = .27).
“This study supports that early NPM1m MRD monitoring in peripheral blood may not only refine the prognostic of this subgroup of patients with acute myeloid leukemia but also be helpful to identify patients who are the best candidates for allogeneic stem cell transplantation,” Balsat and colleagues wrote. “Future efforts should focus on validating the best source of samples to quantify NPM1m MRD and standardizing MRD evaluation.” – by Andy Polhamus
Disclosure: Balsat reports no relevant financial disclosures. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.
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