.
This survival benefit did not extend to patients who were MRD-negative after their second induction therapy, Jad Othman, MBBS, reported at the American Society of Hematology annual meeting.
The findings confirm the value of assessing MRD after induction chemotherapy to help identify patients with NPM1-mutated AML in first complete remission who are more likely to benefit from allogeneic transplant, said Dr. Othman, of King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London, and the University of Sydney, Australia.
Recently, updated European LeukemiaNet recommendations, which stratify patients with AML by favorable, intermediate, and adverse prognoses, now include a revised genetic-risk classification. This classification generally considers NPM1-mutated AML favorable risk. However, having a co-mutation with FLT3-ITD raises the risk to intermediate.
Despite this increased granularity in risk stratification, “it’s still not really clear who should have transplant in first remission with NPM1-mutated AML,” Dr. Othman said. “And there is still significant variation in practice, not just worldwide but even center to center.”
Although accumulating evidence suggests that MRD-negative patients with intermediate-risk AML are unlikely to benefit from allogeneic transplant in first complete remission, the presence of a FLT3-ITD mutation is often considered an indication for transplant, Othman explained. However, most studies supporting this view occurred before the development of sensitive molecular MRD measurement techniques.
The latest findings, from two sequential prospective randomized trials of intensive chemotherapy in adults aged 18-60 years with newly diagnosed AML may help clarify who will probably benefit from transplant and who won’t based on MRD status and relevant molecular features.
The first study (AML17), conducted from 2009 to 2014, selected patients for transplant in first complete remission using a validated risk score that incorporated features including age, sex, and response after therapy. The other (AML19), conducted from 2015 to 2020, selected patients with NPM1-mutated AML for transplant only if they tested positive for MRD in peripheral blood after their second course of treatment, regardless of FLT3-ITD status or other baseline risk factors.
Overall, the current analysis included the 737 patients with NPM1-mutated AML, 348 from AML17 and 389 from AML19, who were in complete remission after two courses of treatment and had an MRD sample at that point.
In AML17, 27% of MRD-positive patients (16 of 60) and 18% of MRD-negative patients (52 of 288) underwent transplant in first complete remission compared with 60% (50 of 83) and 16% (49 of 306), respectively, in AML19.
Among all 737 patients, Dr. Othman and colleagues did not observe an overall survival benefit among those who underwent transplant vs those who did not (hazard ratio [HR], 1.01) or among patients who were MRD-negative (HR, 0.82).
However, patients who were MRD-positive did have a significant survival advantage after transplant (HR, 0.39). In these patients, 3-year overall survival was 61% among those who underwent transplant vs 24% among those who did not.
In MRD-negative patients, transplant in first complete remission did not improve overall survival despite improved relapse-free survival (HR, 0.50). This outcome, Othman explained, probably occurred because most patients who did not undergo transplant and who relapsed were salvaged, with about two thirds undergoing a transplant during their second complete response.
Results in patients with NPM1 FLT3-ITD co-mutation mirrored those in the overall population: MRD-positive patients in first complete remission who underwent transplant demonstrated improved overall survival compared with those without transplant (HR, 0.52), but the overall survival benefit did not extend to MRD-negative patients (HR, 0.80).
The findings show that molecular MRD after induction chemotherapy can identify patients with NPM1-mutated AML who are more likely to benefit from transplant in first remission, Dr. Othman concluded. However, he noted, because only 16% of patients overall were older than 60 years, the results may not be generalizable to older patients.
A version of this article appeared on Medscape.com.