Azacitidine, Venetoclax, Ruxolitinib Shows Encouraging Responses in MPNs


Findings from a 5-patient study evaluating azacitidine, venetoclax, and ruxolitinib for the treatment of myeloproliferative neoplasms shows promise. More research is warranted.

3D rendering of myeloproliferative neoplasm -

3D rendering of myeloproliferative neoplasm -

The combination of azacitidine, venetoclax (Venclexta), andruxolitinib(Jakafi) for the treatment of myeloproliferative neoplasms in blastic phase (MPN-BP) did not demonstrate any treatment-related toxicity in patients, and patients’ quality-of-life improved, according to a study published in the British Journal of Haematology.1

Azacitidine and venetoclax were used to control BP transformation, and ruxolitinib was added to control constitutional symptoms. The overall response rate was 80%, and the complete remission (CR) rate was 40%. The median overall survival was 13.4 months (95% CI, 4.2-13.4), with a median follow-up of 10.0 months (range, 4.2-13.4).

“[Patients with] MPN-BP have a poor prognosis with the current treatment options, and standards of care unless they are offered [allogeneic stem cell transplant, (allo-SCT)]. Unfortunately, there is a lack of treatment guidelines for the management of allo-SCT-ineligible MPN-BP patients,” study authors wrote. “We observed encouraging hematological responses, which were prolonged for some patients. In addition, the combination appeared manageable, without unexpected adverse events.”

Five patients with myelofibrosis (MF) were enrolled in the study. One had primary MF, and 4 had secondary MF. The median patient age was 76 (range, 72-84) years. Three patients were treated exclusively outpatient. There were 2 CRs and 2 partial response remissions. Investigators noted that all patients could complete their activities of daily living, and clinical spleen reduction ≥50% was observed.

At best response, the median platelet count was 150 × 109/L (range, 60–380) with a median improvement of 125 × 109/L (range, 5–200), and median hemoglobin level was 10.6 g/dL (range, 9.0–13.8) with a median gain of 2.7 g/dL (range, 1.5–7.6).

Three patients died due to disease progression; however, there were no deaths due to treatment reported. Observed adverse events (AEs) included neutropenia (n = 4, 80%), anemia (n = 2, 40%), and thrombocytopenia (n = 1, 20%). Febrile neutropenia was reported in 2 patients during the initial cycle. Grade 4 neutropenia was the primary reason reported for postponing a cycle.

Patients were administered ruxolitinib and a dose ≥10 mg twice daily. Venetoclax was administered orally at a dose of 200-400 mg on days 1-14. Azacitidine was administered subcutaneously at a dose of 50 or 75 mg/m2 on days 1-7. The median cycle duration was 29 days (range, 27-38). A median of 11 cycles (range, 5-14) was administered to patients, and the median time to best response was 4 cycles (range, 3-9).


“Further studies are needed to confirm these promising results,” study authors wrote.1

The combination of venetoclax and azacitidine are also being studied in a phase 3 trial of patients with treatment-naïve acute myeloid leukemia, as well as a phase 1 trial of pediatric and young adult patients with hematologic malignancies.2,3

1. Systchenko T, Chomel JC, Gallego-Hernanz P, et al. Combination of azacitidine, venetoclax and ruxolitinib in blast phase myeloproliferative neoplasms. Br J Haematol. 2023;202(2):284-288. doi:10.1111/bjh.18853
2. A study of venetoclax in combination with azacytidine versus azacytidine in treatment naïve participants with acute myeloid leukemia who are ineligible for standard induction therapy. News release.National Cancer Institute. Accessed October 13, 2023. 
3. Venetoclax and azacytidine for the treatment of hematologic malignancies in pediatric and young adult patients. News release. National Cancer Institute. Accessed October 13, 2023.
Related Videos
Related Content