Eprenetapopt plus azacitidine after allogeneic hematopoietic stem-cell transplantation for TP53 -mutant acute myeloid leukemia and myelodysplastic syndromes Journal Article
| Authors: | Mishra, A.; Tamari, R.; DeZern, A. E.; Byrne, M. T.; Gooptu, M.; Chen, Y. B.; Deeg, H. J.; Sallman, D.; Gallacher, P.; Wennborg, A.; Hickman, D. K.; Attar, E. C.; Fernandez, H. F. |
| Article Title: | Eprenetapopt plus azacitidine after allogeneic hematopoietic stem-cell transplantation for TP53 -mutant acute myeloid leukemia and myelodysplastic syndromes |
| Abstract: | PURPOSEOutcomes are poor in TP53-mutant (mTP53) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), even after allogeneic hematopoietic stem-cell transplant (HCT). Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator.PATIENTS AND METHODSWe conducted a phase II, multicenter, open-label trial to assess efficacy and safety of eprenetapopt combined with azacitidine as maintenance therapy after HCT (ClinicalTrials.gov identifier: NCT03931291). Patients with mTP53 MDS or AML received up to 12 cycles of eprenetapopt 3.7 g once daily intravenously on days 1-4 and azacitidine 36 mg/m2 once daily intravenously/subcutaneously on days 1-5 in 28-day cycles. The primary outcomes were relapse-free survival (RFS) and safety.RESULTSOf the 84 patients screened for eligibility before HCT, 55 received a transplant. Thirty-three patients ultimately received maintenance treatment (14 AML and 19 MDS); the median age was 65 (range, 40-74) years. The median number of eprenetapopt cycles was 7 (range, 1-12). With a median follow-up of 14.5 months, the median RFS was 12.5 months (95% CI, 9.6 to not estimable) and the 1-year RFS probability was 59.9% (95% CI, 41 to 74). With a median follow-up of 17.0 months, the median overall survival (OS) was 20.6 months (95% CI, 14.2 to not estimable) and the 1-year OS probability was 78.8% (95% CI, 60.6 to 89.3). Thirty-day and 60-day mortalities from the first dose were 0% and 6% (n = 2), respectively. Acute and chronic (all grade) graft-versus-host disease adverse events were reported in 12% (n = 4) and 33% (n = 11) of patients, respectively.CONCLUSIONIn patients with mTP53 AML and MDS, post-HCT maintenance therapy with eprenetapopt combined with azacitidine was well tolerated. RFS and OS outcomes were encouraging in this high-risk population. © American Society of Clinical Oncology. |
| Keywords: | controlled study; aged; human cell; major clinical study; overall survival; genetics; leukemia, myeloid, acute; clinical trial; constipation; diarrhea; drug efficacy; drug safety; drug withdrawal; side effect; antineoplastic agents; follow up; antineoplastic agent; multiple cycle treatment; phase 2 clinical trial; anemia; nausea; thrombocytopenia; vomiting; maintenance therapy; recurrence; hematopoietic stem cell transplantation; protein p53; abdominal pain; coughing; dizziness; dyspnea; febrile neutropenia; fever; pruritus; myelodysplastic syndrome; multicenter study; graft versus host reaction; tumor suppressor protein p53; recurrent disease; allogeneic hematopoietic stem cell transplantation; headache; graft vs host disease; tp53 protein, human; pericardial effusion; tremor; azacitidine; myelodysplastic syndromes; hypocalcemia; recurrence free survival; decreased appetite; acute myeloid leukemia; dyskinesia; acute graft rejection; chronic graft rejection; humans; human; male; female; article; eprenetapopt |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 40 |
| Issue: | 34 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2022-12-01 |
| Start Page: | 3985 |
| End Page: | 3993 |
| Language: | English |
| DOI: | 10.1200/jco.22.00181 |
| PUBMED: | 35816664 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 January 2023 -- Source: Scopus |
