Table 1.
Currently available therapies and selected emerging therapies for TP53-mutated acute myeloid leukemia and myelodysplastic syndrome
| Agent / Regimen | Study Phase | Population | TP53mut pts | Response | CR rate | Median OS (mo.) | Trial identifier |
|---|---|---|---|---|---|---|---|
| AML | |||||||
| Azacitidine or decitabine | 2, retrospective | ND AML | 22 | CR/CRi 22–38% | 13–22% | 2.1–7.3 | (63–66) |
| Venetoclax + azacitidine or 5-day decitabine | 1b/2 | ND AML | 36 | CR/CRi 41–72% | 20–46% | 4.9–7.2 | NCT02203773(70,71) |
| Venetoclax + 10-day decitabine | 2; post-hoc | ND AML | 26 | ORR 77% | 48% | 5.4 | NCT03404193(126) |
| Magrolimab + azacitidine | 1b | ND AML | 29 | CR/CRi 59% | 45% | 12.9 | NCT03248479(127) |
| Magrolimab + venetoclax + azacitidine | 1b/2 | ND AML | 14 | ORR 86% | 64% | NR | NCT04435691(84) |
| Eprenetapopt + azacitidine | 1b/2 | ND AML | 18 | ORR 33% | 17% | 10.4 | NCT03588078(97) |
| Sabatolimab + HMA | 1b | ND AML | 5 | CR/CRi 40% | 20% | DOR 6.4 | NCT03066648(107) |
| SGN-CD33A ± HMA | 1/2 | ND AML | 7 | CR/CRi 86% | NA | NCT0192329(128) | |
| Nivolumab + intensive chemotherapy | Post-hoc | ND AML | 4 | ORR 50% | NA | NA | NCT02464657(67) |
| Intensive chemotherapy | Retrospective | ND AML | various | ORR 47–55% | 45–55% | 6.8–8.8 | (6,64) |
| Low-intensity chemotherapy | Retrospective | ND AML | various | ORR 14–50% | 36% | 6.7–9.0 | (6,63,64) |
| Flotetuzumab | 1/2 | R/R AML | 15 | ORR 60% | 47% | 4.0 | NCT02152956(90) |
| Nivolumab + azacitidine | 2 | R/R AML | 26 | ORR 23% | NA | NA | NCT02397720(110) |
| Venetoclax + 10-day decitabine | 2; post-hoc | R/R AML | 24 | ORR 46% | 19% | 4.5 | NCT03404193(126) |
| MDS | |||||||
| Azacitidine or decitabine | Post-hoc | MDS | various | ORR 39–100% | 1–32% | 9.4–12.4 | NCT01687400(61,64) |
| Eprenetapopt + azacitidine | 1b/2 | MDS | 40 | ORR 73% | 50% | 10.8 | NCT03072043(96) |
| Sabatolimab + HMA | 1b | MDS | 14 | ORR 71% | 29% | OS not reported (DOR 21.5) | NCT03066648(107) |
OS = overall survival, ND = newly diagnosed, R/R = relapsed or refractory, AML = acute myeloid leukemia, MDS = myelodysplastic syndrome, MPN = myeloproliferative neoplasm, ORR = overall response rate, defined as sum of all responses per the IWG criteria or ELN2017 criteria. CR = complete remission, CRi = CR with incomplete hematologic recovery, mCR = marrow CR, MLFS = morphologic leukemia-free state, DOR = duration of response