Pacritinib + Venetoclax + Azacitidine combination (AP/BP MPN)

Current understanding

A first-in-class triple combination pairing pacritinib (JAK2/IRAK1/FLT3/CSF1R inhibitor) with venetoclax (BCL-2 inhibitor) and azacitidine (hypomethylating agent) for accelerated and blast phase myeloproliferative neoplasms. Currently under phase I evaluation for safety, tolerability, and optimal dosing in this high-unmet-need population with no established standard of care. Rationale is simultaneous targeting of JAK-STAT/NF-κB signaling, apoptosis resistance, and epigenetic dysregulation.

Evidence log

• 2026-09-21 — Metronomic Decitabine-Cedazuridine and Venetoclax in R/R AML, HR-MDS, HR/AP MPN: cross-connection with astx727-cedazuridine-decitabine: Both regimens deploy an HMA + venetoclax backbone in AP/BP MPN; the metronomic ASTX727 + venetoclax study offers an all-oral, JAKi-free comparator to the pacritinib + azacitidine + venetoclax triplet. (novelty: 3)
• 2026-07-01 — Phase I Trial of Pacritinib in Combination With Venetoclax and Azacitidine for the Treatment of Accelerated and Blast Phase Myeloproliferative Neoplasms: cross-connection with ap-bp-mpn-bridging: The new pacritinib + venetoclax + azacitidine triplet is positioned within the emerging AP/BP-MPN bridging landscape, potentially serving as an intensified alternative to JAK inhibitor + HMA doublets for patients pre-transplant. (novelty: 4)

Open questions

Related