The use of small molecule drugs, such as FLT3 inhibitors and isocitrate dehydrogenase inhibitors, is being investigated after promising results for these agents were reported in the relapse setting. Recently, researchers presented final data from the ADMIRAL trial ( Identifier: NCT02014558) that suggested treatment with the gilteritinib, a therapeutic agent that targets FLT3, may significantly improve survival in patients with relapsed or refractory AML who harbor a mutation in FLT3 when compared with standard chemotherapy regimens. A phase 2 study ( Identifier: NCT02927262) is currently under way to assess DFS in patients with FLT3 mutations in CR1 receiving either gilteritinib or placebo for 2 years following completion of induction and consolidation chemotherapy.

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Venetoclax, a highly selective BCL-2 inhibitor, might be considered as a maintenance approach, especially in elderly patients not eligible for intensive chemotherapy and transplant. This drug has been shown to have tolerable safety and favorable overall response rates in combination with HMAs in elderly patients with de novo AML. However, the long-term safety, tolerability, and myelosuppression of venetoclax are still unclear.

Maintenance Therapy Following Transplantation

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Relapse risk in AML following alloHSCT remains a challenge, and outcomes are particularly poor. Post-transplant maintenance therapy can be administered to patients in MRD-negative CR, but it requires the use of small molecule drugs to avoid adverse events and exacerbation of graft-versus-host disease (GVHD).

HMAs have been investigated as agents for maintenance therapy that may decrease relapse after alloHSCT. In a study conducted by the MDACC group, patients with AML in relapse or CR following alloHSCT received low doses of azacitidine. Patients in CR remained in CR for a median of 17 months. However, other trials have shown inconclusive results; some showed no benefit with early treatment discontinuation due to toxicity, while others showed a tendency toward improvements in OS and DFS.

The role of decitabine was evaluated in a phase 1 study that included 17 patients in CR following transplant. The 2-year OS and DFS were 56% and 48%, respectively. The phase 2 LENAMAINT trial investigated the role of lenalidomide in 10 patients with the del5q mutation who underwent transplant, but the trial was ended prematurely due to 6 of the 10 patients developing GVHD.

In the randomized SORMAIN trial, the FLT3 inhibitor sorafenib demonstrated significantly reduced risk for relapse or death in patients with FLT3 internal tandem duplicationpositive AML. After 24 months of sorafenib administration, 2-year DFS was significantly higher in the sorafenib group compared with the placebo group (85% vs 53.3%; P =.0135), and OS was significantly longer in patients receiving sorafenib as well (P =.03). Quizartinib, another FLT3 inhibitor, has also been shown to have good tolerability and reduce relapse rates following HSCT.

The review authors concluded that “the ongoing challenge in AML treatment is finding safe, well tolerated postremission strategies able to reduce the relapse rate and produce more cures.” They noted that maintenance treatment may be particularly helpful for patients in CR after consolidation or HSCT who have “adverse biological characteristics, a poor molecular response to chemotherapies,” or MRD positivity.

Further trials are necessary to assess the benefit of azacitidine, venetoclax, and checkpoint inhibitors on survival and treatment outcomes, particularly in older and MRD-negative patients. Additionally, emerging targeted therapies are being tested, and most new clinical trials on AML treatment include maintenance strategies. Nonetheless, several questions remain unanswered.


1. Molica M, Breccia M, Foa R, Jabbour E, Kadia TM. Maintenance therapy in AML: the past, the present and the future [published online August 19, 2019]. Am J Hematol. doi:10.1002/ajh.25620