A new multicenter phase 2 clinical trial has revealed encouraging results for patients with myelofibrosis, demonstrating that a 10-day treatment course of subcutaneous Dacogen (decitabine) achieved responses in one-third of treated patients.
Clinical Trial Results and Patient Outcomes
The study, published in Blood Advances, evaluated 21 patients who received daily subcutaneous Dacogen at a dose of 0.3 milligrams per kilogram. Seven patients achieved a clinical response, resulting in an overall response rate of 33%. The median duration of response was seven months, with a median time to response of two months.
Among the responding patients, one achieved a partial response, while four demonstrated an anemia response according to the 2013 revised International Working Group response criteria. Two of these patients also met the criteria for a spleen response.
Patient Population and Treatment Details
The study population included patients with a median age of 67 years, with 57% being male. At baseline, 12 patients had transfusion-dependent anemia, and 18 presented with splenomegaly. Fourteen patients had undergone previous treatments for myelofibrosis.
A total of 101 treatment cycles were administered across the patient cohort, with a median of four cycles per patient. Eighteen of the 21 participants completed at least two cycles of therapy.
Safety Profile and Adverse Events
The treatment regimen demonstrated significant myelosuppressive effects:
- 71% of patients experienced grade 3 or 4 neutropenia
- 76% developed grade 3 or 4 anemia
- 62% showed grade 3 or 4 thrombocytopenia
- 48% experienced febrile neutropenia
Common non-hematologic adverse events included:
- Fatigue (62%)
- Hypocalcemia (38%)
- Anorexia (38%)
- Elevated alkaline phosphatase (33%)
- Hyperglycemia (33%)
- Hypoalbuminemia (33%)
- Infection (33%)
More severe grade 3 and 4 non-hematologic toxicities were observed in some patients, with four experiencing infections and three developing bleeding complications. One patient with baseline blast phase myelofibrosis died due to sepsis.
Predictive Factors for Treatment Response
Researchers identified several factors associated with positive treatment response, including:
- High International Prognostic Scoring System risk score
- Elevated baseline fetal hemoglobin levels
- Sustained decrease in circulating CD34+ cell counts
Clinical Significance
"The arsenal of currently available treatments for myelofibrosis is limited and primarily supportive," the researchers noted. This study represents the first prospective evidence supporting the feasibility and efficacy of a low-dose, extended schedule of subcutaneous Dacogen in myelofibrosis patients.
While the results demonstrate potential in treating cytopenias associated with myelofibrosis, the significant myelosuppression observed suggests that further investigation of alternative dosing schedules may be necessary to optimize the treatment approach.
