Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms
Key claim: A phase II trial is evaluating whether decitabine combined with ruxolitinib, fedratinib, or pacritinib as pre-transplant bridging therapy is superior to multi-agent chemotherapy or no pre-transplant therapy in accelerated/blast phase MPN patients.
Abstract
This phase II trial studies how well decitabine with ruxolitinib, fedratinib, or pacritinib works before hematopoietic stem cell transplant in treating patients with accelerated/blast phase myeloproliferative neoplasms (tumors). Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ruxolitinib, fedratinib, and pacritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy before a donor hematopoietic stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient’s bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient’s immune cells and help destroy any remaining cancer cells. Decitabine, with ruxolitinib, fedratinib, or pacritinib may work better than multi-agent chemotherapy or no pre-transplant therapy, in treating patients with accelerated/blast phase myeloproliferative neoplasms.
Why this matters
AP/BP MPN patients have dismal outcomes and no standard pre-transplant bridging regimen, leaving clinicians to choose between AML-like chemotherapy, hypomethylating agents, or proceeding directly to transplant. This phase II trial directly addresses that gap by testing decitabine + JAK inhibitor combinations head-to-head against chemotherapy and no bridging, and could reshape transplant referral decisions for advanced-phase disease if the combination achieves better disease control without compromising transplant fitness.