{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:05:06Z","timestamp":1786964706816,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n Relapsed or refractory AML (R\/R-AML) remains a particularly adverse population necessitating improved therapeutic strategies. In this phase 1 study, we evaluated the efficacy and safety of chidamide, azacitidine, cytarabine, aclarubicin and granulocyte colony-stimulating factor (CACAG) in combination with the B cell lymphoma-2 inhibitor venetoclax (VEN) in R\/R-AML.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a phase 1 trial to assess the safety and efficacy of CACAG-VEN regimen as a salvage induction regimen for patients with R\/R AML. The primary endpoint was the treatment-related adverse events and overall response rate (ORR) following one cycle of the CACAG-VEN regimen. We also performed single-cell RNA sequencing on eight samples of bone marrow from four patients before and after CACAG-VEN treatment.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n From January 10, 2022, to June 8, 2024, the median follow-up was 461 days (range: 180\u2013985 days). Thirty-four patients with refractory (n = 17) and relapsed (n = 17) AML were enrolled. The ORR was 76.5%, and the complete response rate was 73.5%. In patients with composite complete response (CRc), 44% of patients attained a measurable residual disease negative status, the 1-year overall survival (OS) rate was 82.3% (95% CI: 67.8\u201399.9%) and the progression-free survival rate (PFS) was 79.8%. After one cycle of CACAG-VEN, 44.1% (n = 15) of patients developed grade 3\u20134 myelosuppression. The median durations of neutropenia and thrombocytopenia were 17 days (95% CI: 15\u201322 days) and 24 days (95% CI: 22\u201341 days), respectively. Single-cell RNA sequencing revealed that post-treatment downregulation of MCL1, HIF1A, and ABCC1, highlighting the multi-targeted action of the regimen. Furthermore, treatment response was associated with the suppression of mitochondrial activity and the activation of the p53 signaling pathway.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In patients with R\/R AML, the CACAG-VEN regimen resulted in significant clinical benefits, with a high CRc rate and encouraging survival, as well as being well tolerated.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n https:\/\/www.chictr.org.cn\/<\/jats:ext-link>\n , identifier, ChiCTR2200065634\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1698710","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T06:30:13Z","timestamp":1765434613000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Phase 1 study of chidamide in combination with venetoclax, azacitidine, aclarubicin, cytarabine and G-CSF for refractory\/relapsed acute myeloid leukemia: 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