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The combination of ruxolitinib and azacitidine is well tolerated with good responses in patients with myelofibrosis

Ruxolitinib is effective in controlling symptoms and organomegaly in patients with myelofibrosis (MF) and the combination with azacitidine may further improve its efficacy. Indeed the data presented by Daver et al demonstrated that the combination is safe, had promising IWG-MRT 2013 objective responses (73% of the patients) and spleen reduction by >50% in 68% and 59% of the patients at any time on study, and at week 24, respectively.

At EHA 2018, this single institutional, prospective, non-randomized, phase II study was presented. In this study patients were treated continuously with ruxolitinib 15 or 20 mg orally twice daily since cycle 1. Azacitidine was given 25 to 75 mg/m2 on days 1-5 of each 28-day cycle and was added starting at cycle 4. Responses were assessed per International Working Group for Myelofibrosis Research and Treatment 2013 criteria (IWG-MRT).

In this study 52 patients were enrolled and the median age of the patients was 66 years (range: 48-87), 65% of the patients had int-2/high DIPSS score, 40 (77%) had spleen ≥5cm, 30 (58%) were JAK2V617F positive and 27 patients (52%) were previously treated.

Thirty-eight patients (73%) achieved an IWG-MRT 2013 objective response. In total, 26 (65%), 23 (58%) and 25 (63%) patients had palpable spleen reduction by >50% at any time on study, at week 24, and at week 48, respectively. IWG-MRT 2013 objective responses occurred after additions of azacitidine in 7 patients with a median time of 2.0 months from start of azacitidine treatment.

Bone marrow biopsies of 31 patients were available for sequential evaluation. Of these patients 19 (61%) had a documented improvement in bone marrow fibrosis by at least one grade per European grading (EUMNET), with median time to first documented fibrosis improvement of 12 months (range: 6-18).

Overall, 31 patients (63%) experienced grade 3/4 toxicity while on therapy. New onset of G3/4 anemia, thrombocytopenia and neutropenia occurred in 31%, 23% and 21% of patients, respectively. Only 4 patients (8%) discontinued therapy due to toxicities. The most common reasons for therapy discontinuation were elective stem cell transplantation (n=12), and uncontrolled disease (n=8), including progression to AML in 4 patients.

In conclusion, concomitant ruxolitinib with azacitidine was well tolerated with an overall IWG-MRT response rate of 73%, and  >50% spleen reduction in 58% of the patients at week 24. Moreover, 52% of patients achieved an objective improvement in bone marrow fibrosis grade with a median time to improvement of 12 months, which compares favorably to treatment with only ruxolitinib.



Masarova L, Verstovsek S, Cortes J, et al. Phase 2 study of ruxolitinib in combination with 5-azacitidine in patients with myelofibrosis. Presented during EHA 2018; Abstract S812.

Spreker Naval Daver


Naval Daver, MD, PhD, MD Anderson Cancer Center, Houston, United States


Zie: Keyslides


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