Integrating MRD kinetics with allogeneic SCT decisions in AML

TO THE EDITOR:

We thank Rodríguez-Arbolí et al¹ for their interest in our study on the impact of measurable residual disease (MRD) kinetics on outcomes of acute myeloid leukemia (AML).²

Regarding their question about referral patterns for allogeneic stem cell transplant (SCT) in our cohort, it is our practice to refer all newly diagnosed patients with AML aged <75 years with adequate organ function and performance status for consideration of SCT in first remission. During the period of this retrospective analysis, responding patients with available donors and intermediate- or adverse-risk disease were typically recommended to undergo SCT. Accordingly, the characteristics of transplanted vs nontransplanted patients in our study were largely similar, except for a higher rate of FLT3-internal tandem duplication mutations in the transplanted cohort (51% vs 26%; P < .01). With emerging data on impact of high-sensitivity NPM1 and FLT3-internal tandem duplication next-generation sequencing MRD assays,3, 4, 5 the risk/benefit calculation of SCT is changing, and we are now deferring SCT for most patients who achieve rapid and deep MRD negativity by these assays, along with close MRD monitoring.

The ETAL-1 and AML17/19 studies also evaluated the role of allogeneic SCT in patients with AML and found no benefit of SCT for patients with intermediate-risk cytogenetics⁶ or those with NPM1^mut who achieved molecular MRD negativity.³ The differences in results between these studies and ours may be due to several factors. For example, our practice is to induce most fit patients with a regimen consisting of idarubicin and dose-intensified cytarabine, with or without the addition of a purine analog and/or venetoclax.⁷ Since the late 2000s, we also added a FLT3 inhibitor to most patients with FLT3^mut AML. With our frontline approach, our relapse rate is lower than that reported in many large multicenter studies; however, the relapses that do occur are enriched with complex cytogenetics, TP53^mut and abn(17p), even in patients with intermediate risk disease at diagnosis.7, 8, 9 Because patients who relapse after our more intensive frontline therapy may be more challenging to bridge to allogeneic SCT in second remission, this may at least partially explain why we found a benefit to consolidative SCT in first remission in MRD-negative intermediate-risk patients, whereas some other studies have not.

The question of who can be treated without consolidative SCT remains an area of active investigation, but with improved frontline and salvage therapies and high-sensitivity MRD monitoring, we hope that the role of allogeneic SCT for intermediate-risk AML in first remission will fade in the not-too-distant future.

Conflict-of-interest disclosure: The authors declare no competing financial interests.