Prognostic Value of MRD in AML Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation in First versus Second Morphologic Remission

This retrospective analysis was conducted in a large academic medical center in Germany to gain insights into the prognostic value of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) who underwent allogeneic stem-cell transplantation (allo-SCT) consolidation after first morphologic complete remission (CR)/CR with incomplete recovery (CRi) (CR1/CR1i) or after second CR/CRi (CR2/CR2i) achieved following first relapse. Communicated results from this study are summarized here.

The authors identified 580 patients with AML who underwent allo-SCT consolidation; of these, 79% were in first CR and 21% were in CR2. The majority of these patients proceeded to hematopoietic stem-cell transplantation at CR1/CR1i (79%). The median age of the study cohort was 59.6 years; most patients received nonmyeloablative (66%) conditioning regimens, followed by myeloablative (28%) regimens. Median follow-up after allo-SCT was 3.9 years.

Although patients transplanted in CR2/CR2i had better disease risk at diagnosis, they had worse prognosis than those transplanted in CR1/CR1i. When compared with patients transplanted in CR1/CR1i, patients in CR2/CR2i had a significantly lower likelihood of having been diagnosed with secondary AML (P = .002), lower incidence of monosomal (P <.002) or complex (P <.001) karyotype, a higher likelihood of having a normal karyotype (P <.001), and a higher likelihood of harboring NPM1 mutations (P = .001) as well as FLT3 internal tandem duplication (ITD; P = .04) at diagnosis. Compared with patients transplanted in CR1/CR1i, patients in CR2/CR2i were administered a significantly lower number of chemotherapy cycles prior to allo-SCT (71% of patients received ≥1 cycles from relapse to allo-SCT) than those in CR2/CR2i (61% of patients received ≥2 cycles from diagnosis to allo-SCT). However, compared with patients transplanted in CR1/CR1i, patients transplanted in CR2/CR2i showed a trend for MRD-positive disease (P = .10), had a significantly higher cumulative incidence of relapse (CIR; P <.001), and significantly shorter event-free survival (EFS; P = .002).

The MRD status at the time of allo-SCT was an important prognostic factor for CIR and EFS in both patient cohorts, with MRD positivity linked to adverse outcomes. However, MRD-positive patients transplanted in CR1/CR1i had comparable CIR and EFS outcomes as MRD-negative patients transplanted in CR2/CR2i, thus highlighting the worse outcomes of transplantation in CR2/CR2i. In the European LeukemiaNet intermediate-risk patient cohort, both MRD-negative patients transplanted in first or second CR/CRi had favorable outcomes in terms of CIR and EFS, while MRD-positive patients transplanted in CR1/CR1i showed modest outcomes, and MRD-positive patients transplanted in CR2/CR2i experienced poor outcomes.

Based on these results, it was concluded that MRD status at allo-SCT and the number of remissions prior to transplantation were important independent prognostic factors in patients with AML.

Source: Jentzsch M, et al. ASH 2021; abstr 416.