Table 2 Broad indications and common treatment-related adverse events of marketed epigenetic-targeting drugs
From: Epigenetics-targeted drugs: current paradigms and future challenges
Drug(s) | Target(s) | Route(s) of administration | FDA approval | EMA/NMPA approvals | Broad indications | Common grades 3 or worse treatment-related adverse effects reported in clinical trials | Reference(s) |
|---|---|---|---|---|---|---|---|
Azacitidine | DNMT1 | Intravenous/subcutaneous | Yes | — | Juvenile myelomonocytic leukemia | Thrombocytopenia, neutropenia, anemia, sepsis, infection, and pneumonia | |
Subcutaneous | Not approved yet | EMA | AML; CMML; MDS | ||||
Intravenous | Not approved yet | NMPA | AML; MDS; Philadelphia chromosome positive CML | ||||
Oral azacitidine | DNMT1 | Oral | Yes | — | AML | Febrile neutropenia, thrombocytopenia,leukopenia, pneumonia, respiratory failure, bacteraemia, and sepsis | |
Decitabine | DNMT1 | Intravenous | Yes | NMPA | MDS | Febrile neutropenia, thrombocytopenia, anemia, pneumonia, and infection | |
Intravenous | Yes | — | CMML; Refractory anemia (with/without) excess blasts | ||||
Intravenous | Not approved yet | EMA | AML | ||||
Decitabine/Cedazuridine | DNMT1, CDA | Oral | Yes | — | MDS | Thrombocytopenia, febrile neutropenia, pneumonia, respiratory failure, bacteraemia, and sepsis | |
Oral | Not approved yet | EMA | AML | ||||
Vorinostat | HDACs | Oral | Yes | — | CTCL | Cellulitis, pulmonary embolism, sepsis, anorexia, increased creatinine phosphokinase, rash, and thrombocytopenia | |
Romidepsin | HDACs | Intravenous | Yes | — | CTCL; PTCL | Lymphopenia, neutropenia, leukopenia, thrombocytopenia, infections, and tumor lysis syndrome | |
Belinostat | HDACs | Intravenous | Yes | — | PTCL | Anemia, thrombocytopenia, dyspnea, neutropenia, infections, tumor lysis syndrome, and ventricular fibrillation | |
Panobinostat | HDACs | Oral | Canceled by the FDA in 2022 | EMA | MDS | QTc prolongation, hemorrhage, thrombocytopenia, lymphopenia, and asthenia | |
Chidamide | Class I HDAC | Oral | Not approved yet | NMPA | Breast cancer; DLBCL; PTCL | Neutropenia, thrombocytopenia, anemia, leukopenia, diarrhea, and mucositis | |
Givinostat | HDAC1, HDAC3 | Oral | Yes | — | DMD | Diarrhea | |
Enasidenib | IDH2 | Oral | Yes | — | AML | Febrile neutropenia, IDH differentiation syndrome, and indirect hyperbilirubinemia | |
Ivosidenib | IDH1 | Oral | Yes | NMPA | AML | QT interval prolongation, IDH differentiation syndrome, anemia, and ascites | |
Oral | Yes | — | Cholangiocarcinoma; MDS | ||||
Oral | Not approved yet | EMA | IDH1-mutated AML; IDH1-mutated cholangiocarcinoma | ||||
Ivosidenib/Azacitidine | IDH1/DNMT1 | Oral; intravenous/subcutaneous | Yes | — | IDH1-mutated AML | Febrile neutropenia, neutropenia, bleeding events, infection, IDH differentiation syndrome, and QT interval prolongation | |
Olutasidenib | IDH1 | Oral | Yes | — | IDH1-mutated AML | Thrombocytopenia, febrile neutropenia, anemia, alanine aminotransferase increased, and aspartate aminotransferase increased | |
Tazemetostat | EZH2 | Oral | Yes | — | FL; Sarcoma | Hyperglycemia, hyponatremia, anemia, thrombocytopenia, neutropenia, lymphopenia, and weight loss | |
Valemetostat tosilate | EZH2/EZH1 | Oral | Not approved yet | *Only approved by the PMDA in Japan | ATL | Thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia |
