Azacitidine + Venetoclax combination (higher-risk CMML)

Current understanding

Doublet of the hypomethylating agent azacitidine with the BCL-2 inhibitor venetoclax, an established regimen in AML, now being formally evaluated in higher-risk chronic myelomonocytic leukemia (CMML) — an MDS/MPN overlap subtype with limited treatment options. The phase II single-arm multicenter AVENHIR trial provides trial-early evidence for efficacy and safety in this population.

Evidence log

• 2026-09-11 — A Study to Assess Safety and Preliminary Efficacy of LP-108 Combined With Azacitidine In Subjects With AML, MDS, CMML: cross-connection with lp-108-azacitidine-combination: LP-108 + azacitidine is the LP-108 analog of the established venetoclax + azacitidine backbone in CMML/MDS/AML. (novelty: 3)
• 2026-07-01 — Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML): A Phase 2 Expansion: cross-connection with ruxolitinib-cmml: Both represent emerging systemic therapy approaches in higher-risk CMML, positioning JAK inhibition alongside HMA + BCL-2 inhibitor combinations in the CMML treatment landscape. (novelty: 3)
• 2026-06-05 — A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts: cross-connection with cladribine-cytarabine-venetoclax-azacitidine-cmml-mds: Both regimens deploy the azacitidine + venetoclax backbone in higher-risk CMML; the alternating cladribine/LDAC + venetoclax cycles represent an intensified strategy layered onto the established HMA + BCL-2 doublet. (novelty: 3)
• 2026-06-05 — Venetoclax and Azacitidine for the Treatment of Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia: A phase I/II trial is evaluating safety, optimal dosing, and efficacy of azacitidine + venetoclax specifically in patients with relapsed/refractory high-risk MDS or CMML, extending the HMA + BCL-2 backbone into a difficult-to-treat post-failure population (evidence: trial-early). (novelty: 3)
• 2026-05-29 — Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia: cross-connection with azacitidine-lenalidomide-vorinostat-mds-cmml: Both trials evaluate azacitidine-based combinations in higher-risk CMML; lenalidomide/vorinostat add-on versus venetoclax add-on represent alternative strategies layered on the same HMA backbone. (novelty: 3)
• 2026-05-20 — Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN: cross-connection with fludarabine-busulfan-conditioning: Same trial deploys the azacitidine + venetoclax doublet as a post-transplant maintenance arm following venetoclax-augmented FluBu conditioning, connecting CMML-focused HMA + BCL-2 therapy to the allo-SCT conditioning pathway. (novelty: 3)
• 2026-05-13 — Venetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm: cross-connection with astx727-cedazuridine-decitabine: Both trials test the HMA + venetoclax backbone in CMML/MDS-MPN; ASTX727 + venetoclax provides an all-oral analogue to the AVENHIR (azacitidine + venetoclax) regimen. (novelty: 3)
• 2026-04-16 — Azacitidine and Quizartinib for the Treatment of Myelodysplastic Syndrome or Myelodysplastic/Myeloproliferative Neoplasm With FLT3 or CBL Mutations: cross-connection with azacitidine-quizartinib-combination: Both target higher-risk MDS/MPN-spectrum disease with an azacitidine backbone but use different second agents (FLT3i quizartinib in FLT3/CBL-mutated cases vs. venetoclax in higher-risk CMML), informing molecularly-stratified treatment selection. (novelty: 3)
• 2026-04-23 — A Study of BGB-11417 in Participants With Myeloid Malignancies: cross-connection with bgb-11417-bcl2-inhibitor-myeloid: Both pair a BCL-2 inhibitor with azacitidine; BGB-11417 + azacitidine in MDS/MPN overlap parallels the venetoclax + azacitidine paradigm in CMML. (novelty: 3)
• 2026-03-05 — Azacitidine Combined With Venetoclax in Patients With Higher-risk Chronic Myelomonocytic Leukemia (AVENHIR): cross-connection with azacitidine-venetoclax-gilteritinib-combination: AVENHIR tests the doublet backbone in higher-risk CMML; the triplet study layers gilteritinib on the same backbone in FLT3-mutated advanced myeloid neoplasms including CMML. (novelty: 3)

Open questions

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