Decitabine and Gemtuzumab Ozogamicin In Patients with Advanced Myelofibrosis

While hypomethylating agents, azacitidine and decitabine, are approved for use in treatment of myelodysplastic syndromes (MDS), their role in treatment of myeloproliferative disorders is evolving. The modified dosing schedule of decitabine (20 mg/m² IV for 5 days) in MDS has shown overall response rates of approximately 40%. A clinical study of azacitidine in myelofibrosis (MF) has shown a response rate of 32%. We investigated the activity of the combination of decitabine and gemtuzumab ozogamicin (GO) (anti-CD33 antibody), a combination with activity in patients with MDS and acute myelogenous leukemia (AML), in patients with advanced myelofibrosis.

We reviewed the records of patients with MF treated with the combination of decitabine and GO.

Seven patients were treated till the decisions by FDA to withdraw GO from the market. Age ranged from 60–69 years (median 65 years), 5 patients were male and no of prior therapies ranged 0–4 (median2). Three patients had MF progressed to acute myeloid leukemia. Prior treatments included, hydroxyura, thalidomide, prednisone, pomolidamide etc. All patients were positive for JAK 2 V617F mutation. Cytogenetic abnormalities were seen in 4 patients (hyperdiploid, complex or -5/-7) and 3 were with diploid cytogenetics. Five patients received 3 cycles of Decitabine plus myelotarg while 2 patients had only one cycle. Four patients had stable disease, one had clearance of marrow blasts (40%>0%), two had no response. Three patients showed decreases in splenic size. Clinically significant infectious complications were encountered in 4 patients.

The combination of decitabine and GO showed early signs of activity in patients with MF but future investigation of this combination will be limited due to lack of access to GO.

Borthakur:eisai: Research Funding.