Individualized decitabine dosing for post-HSCT maintenance in MDS and secondary AML from MDS: long-term outcomes from...

Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) remains a major clinical challenge in higher-risk myelodysplastic neoplasms (MDS). Although hypomethylating agents have been evaluated as posttransplant maintenance therapy, their efficacy remains uncertain.

We aimed to evaluate the long-term clinical outcomes of individualized decitabine maintenance therapy following HSCT in patients with MDS or secondary acute myeloid leukemia from MDS.

This was a retrospective comparative study based on a long-term follow-up of the phase I PODAC trial, which individualized posttransplant decitabine maintenance dosing.

Nineteen PODAC participants were included in the treatment group and compared with 52 matched control patients selected through target trial emulation using identical eligibility criteria.

For the 19 PODAC participants, a median of 6 cycles was administered, starting at 5 mg/m²/day and escalating to a median maintenance dose of 7 mg/m²/day. After a median follow-up of 11.4 years in the PODAC group and 9.7 years in the control group (p = 0.90), no significant differences were observed between the two groups in overall survival, relapse-free survival, graft-versus-host disease (GVHD)-free relapse-free survival, or the incidence of relapse, nonrelapse mortality, and grades II-IV acute GVHD. However, the incidence of moderate-to-severe chronic GVHD was significantly lower in the PODAC group and decitabine maintenance emerged as an independent predictor for longer chronic GVHD-free relapse-free survival (cCRFS).

Decitabine maintenance using an adaptive dosing approach enabled prolonged treatment and was associated with a lower incidence of chronic GVHD and improved cGRFS. However, it did not improve survival or relapse outcomes compared to the control group.