Major monotherapy trials of epigenetic-directed therapies
| Class . | Agent . | Trial phase . | Target population . | Patients, n . | Response rate . | Identifier . |
|---|---|---|---|---|---|---|
| HMA | Decitabine vs treatment choice | 3 | Newly diagnosed AML ineligible for intensive chemotherapy | 485 | 17.8% vs 78% CR/CRp, respectively. | NCT00260832 |
| HMA | Azacitidine/decitabine vs intensive chemotherapy | Retrospective* | Newly diagnosed AML | 671 | 28% vs 42% CR, respectively† | NCT00926731, NCT00952588 |
| HMA | Guadecitabine | 2 | R/R AML | 103 | 23% CR/CRi | NCT01261312 |
| HMA | Guadecitabine | 2 | Treatment-naive AML ineligible for intensive chemotherapy | 107 | 57% CR/CRi/CRp | NCT01261312 |
| HMA | Azacitidine vs conventional care | 3 | Newly diagnosed AML with 20-30% blasts ineligible for intensive chemotherapy | 113 | 18% vs 16% CR, respectively (P = .80). | NCT00071799 |
| HMA | Azacitidine vs conventional care | 3 | Newly diagnosed AML with > 30% blasts ineligible for intensive chemotherapy | 488 | 27.8% vs 25.1% CR/CRi, respectively (P = 0.54)‡ | NCT01074047 |
| HDACi | Vorinostat | 2 | R/R AML or newly diagnosed AML ineligible for chemotherapy | 37 | 2.7% CR | NCT00305773 |
| mIDH inhibitor | Enasidenib | 1/2 | IDH2-mutated R/R AML | 239 | 19.3% CR, 6.8% CRi/CRp | NCT01915498 |
| mIDH inhibitor | Ivosidenib | 1 | IDH1-mutated R/R AML | 125 | 21.6% CR, 8.8% CRh | NCT02074839 |
| BET inhibitor | GSK525762 | 1 | R/R AML | 46 | 2.2% CRi, 2.2% CRp | NCT01943851 |
| BET inhibitor | ABBV-075 (mivebresib) | 1 | R/R AML | 19 | 5.3% CRp, preliminary data | NCT02391480 |
| BET inhibitor | OTX015 | 1 | R/R AML and AML ineligible for intensive chemotherapy | 36 | 2.8% CR, 33.3% CRp | NCT01713582 |
| DOT1L inhibitor | EPZ-5676 (pinometostat) | 1 | Pediatric R/R MLL rearranged AML | 18 | No complete responses observed | NCT02141828 |
| Class . | Agent . | Trial phase . | Target population . | Patients, n . | Response rate . | Identifier . |
|---|---|---|---|---|---|---|
| HMA | Decitabine vs treatment choice | 3 | Newly diagnosed AML ineligible for intensive chemotherapy | 485 | 17.8% vs 78% CR/CRp, respectively. | NCT00260832 |
| HMA | Azacitidine/decitabine vs intensive chemotherapy | Retrospective* | Newly diagnosed AML | 671 | 28% vs 42% CR, respectively† | NCT00926731, NCT00952588 |
| HMA | Guadecitabine | 2 | R/R AML | 103 | 23% CR/CRi | NCT01261312 |
| HMA | Guadecitabine | 2 | Treatment-naive AML ineligible for intensive chemotherapy | 107 | 57% CR/CRi/CRp | NCT01261312 |
| HMA | Azacitidine vs conventional care | 3 | Newly diagnosed AML with 20-30% blasts ineligible for intensive chemotherapy | 113 | 18% vs 16% CR, respectively (P = .80). | NCT00071799 |
| HMA | Azacitidine vs conventional care | 3 | Newly diagnosed AML with > 30% blasts ineligible for intensive chemotherapy | 488 | 27.8% vs 25.1% CR/CRi, respectively (P = 0.54)‡ | NCT01074047 |
| HDACi | Vorinostat | 2 | R/R AML or newly diagnosed AML ineligible for chemotherapy | 37 | 2.7% CR | NCT00305773 |
| mIDH inhibitor | Enasidenib | 1/2 | IDH2-mutated R/R AML | 239 | 19.3% CR, 6.8% CRi/CRp | NCT01915498 |
| mIDH inhibitor | Ivosidenib | 1 | IDH1-mutated R/R AML | 125 | 21.6% CR, 8.8% CRh | NCT02074839 |
| BET inhibitor | GSK525762 | 1 | R/R AML | 46 | 2.2% CRi, 2.2% CRp | NCT01943851 |
| BET inhibitor | ABBV-075 (mivebresib) | 1 | R/R AML | 19 | 5.3% CRp, preliminary data | NCT02391480 |
| BET inhibitor | OTX015 | 1 | R/R AML and AML ineligible for intensive chemotherapy | 36 | 2.8% CR, 33.3% CRp | NCT01713582 |
| DOT1L inhibitor | EPZ-5676 (pinometostat) | 1 | Pediatric R/R MLL rearranged AML | 18 | No complete responses observed | NCT02141828 |
2-HG, 2-hydroxyglutarate; 5hmc, 5-hydroxymethylcytosine; α-KG, α-ketoglutarate; Ac, acetyl; BET, bromodomain extraterminal protein; C, cytosine; CRh, CR with partial hematologic recovery; CRp, CR with incomplete platelet recovery; DNMT, DNA methyltransferase; DOT1L, disruptor of telomeric silencing 1-like; EZH, enhancer of zeste homolog; HDAC, histone deacetylase; LSD1, lysine-specific demethylase 1; Me, methyl; mIDH, mutant isocitrate dehydrogenase 1; MLL, mixed lineage leukemia.
One retrospective study was included that had significant implications for AML treatment.
Despite lower CR, median survival was similar compared with intensive chemotherapy.
Despite similar CR, median survival was higher with azacitidine.