Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis

Abstract

IntroductionHypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute myeloid leukemia (AML) patients.Materials and MethodsThe Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases were independently searched by two investigators to identify relevant studies published inception to 18 November 2021. These trials compared HMA maintenance to observation following allo-SCT for AML or myelodysplastic syndrome.ResultsThe meta-analysis eligibility criteria were fulfilled by 14 studies. The overall survival and relapse-free survival of the HMA maintenance group were superior to the observation group, with a pooled risk ratio (RR) of 1.38 and 1.46, respectively. Moreover, the cumulative incidence of relapse was significantly lower in those who received HMAs. The HMA group also had lower non-relapse mortality compared with the observation group. Overall, the incidences of grades III–IV acute graft-vs.-host disease (GVHD) and chronic GVHD did not differ in both groups. However, when looking specifically at those receiving decitabine maintenance, the rate of chronic GVHD seemed to be lower compared with observation alone.ConclusionsThe current systematic review and meta-analysis illustrated that AML and MDS patients receiving HMA maintenance after allo-SCT had better outcomes in regards to OS, RFS, NRM, CIR as well as a reduced incidence of chronic GVHD.

Maintenance therapy in acute myeloid leukemia: advances and controversies

“…A meta-analysis including 14 studies (not limited to randomized controlled trials) showed favorable benefits of post-HSCT HMA maintenance with regard to RFS and OS as well as reduction in rates of chronic GvHD. 109 …”

“…A meta-analysis including 14 studies (not limited to randomized controlled trials) showed favorable benefits of post-HSCT HMA maintenance with regard to RFS and OS as well as reduction in rates of chronic GvHD. 109 An important development was the recently reported, encouraging result on the use of eprenetapopt in combination with azacitidine as maintenance therapy in TP53-mutated MDS/AML patients after HSCT. The combination, planned to be given for 12 cycles administered every 4 weeks, led to a median RFS of 12.5 months and OS of 20.6 months (at a median follow-up of 17 months) in 33 patients (79% previously exposed to HMA, 36% with active disease at the time of HSCT, 83% with persistent TP53 mutation at HSCT) who received this maintenance.…”

Azacitidine and lenalidomide combination: a novel relapse prophylaxis regimen after allogeneic hematopoietic stem-cell transplantation in patients with acute myeloid leukemia

“…The median CD34 + cells numbers for transplantation was 7×10 6 /kg (2.86-11.57). The median time to neutrophil engraftment (≥0.5×10 9 /L) after transplantation was 15 (10-23) days, while that of platelet engraftment (≥20×10 9 /L) was 16 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) days (Table 1).…”

“…However, because LEN can activate NK cells and T cells, it has been reported that the use of LEN may cause severe graft-versus-host disease (GVHD) in patients after allo-SCT ( 10 , 11 ). On the other hand, AZA can accelerate reconstitution of T regulatory cells after transplantation, induce immune tolerance, and reduce the risk of GVHD ( 12 , 13 ). Therefore, we hypothesized that combination of AZA and low-dose LEN could simultaneously provide anti-leukemic activity after transplantation without increasing, overall, the risk of severe GVHD.…”

MRD positivity was the poor prognostic factor for adverse-risk AML patients with allogeneic hematopoietic stem cell transplantation: a multicenter TROPHY study

“…Many studies had identified the efficacy of maintenance therapy in high-risk AML patients [ 21 – 23 ], but the results were somewhat controversial. For example, some reported that sorafenib maintenance can decrease relapse and improve LFS after allo-HSCT [ 24 ]; however, MORPHO trial reported that relapse-free survival and OS were comparable between patients with and without gilteritinib maintenance, and gilteritinib maintenance might only improve the survival of patients who were MRD positivity before allo-HSCT [ 25 ].…”