• Documented informed consent of the participant and/or legally authorized representative

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

⁃ If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Eastern Cooperative Oncology Group (ECOG) =\< 2 or Karnofsky performance status (KPS) \>= 70

• Recipients of allogeneic HCT - all stem cell sources including sibling, unrelated, mismatched related/unrelated, cord and haploidentical transplant patients will be included

• Conditioning regimen: Investigator's choice based on center guidelines

• GvHD prophylaxis: sirolimus + tacrolimus or tacrolimus + methotrexate or investigator choice

• Patients must have acute myeloid leukemia (AML) with IDH2 mutation at diagnosis. Day 30 marrow post HCT should show evidence of morphologic remission with \< 5% bone marrow blasts. Patients with MRD either by flow cytometry or IDH2 mutation testing will be allowed

• Patients with previous therapy with IDH2 inhibitors will be included

• Absolute neutrophil count (ANC) \> 1000 (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

• Hemoglobin \>= 9.5 gm% (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

• Platelets \> 50,000/mm\^3 (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

⁃ NOTE: Patients with lower counts can enroll if infection cytomegalovirus (CMV)/human herpesvirus 6 (HHV6) etc. is being treated actively

• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

• Total bilirubin \< 2.0 mg/dl-exception permitted in patients with Gilbert's Syndrome (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

• Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x ULN, patients with abnormal liver function tests (LFTs) in the context of active GVHD will not be included (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

• Creatinine clearance of \>= 40/min/1.73 m\^2 for participants with creatinine levels above institutional normal per 24 hour urine test or the Cockcroft-Gault formula (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)

• Corrected QT (QTc) =\< 480 ms

⁃ Note: To be performed within 28 days prior to day 1 of protocol therapy

• Seronegative for human immunodeficiency virus (HIV) antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin \[RPR\])

⁃ If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

⁃ If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy

⁃ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)