A Phase II Trial of Azacitidine (NSC-102816) and Gemtuzumab Ozogamicin (NSC-720568) As Induction and Post-Remission Therapy in Patients of Age 60 and Older with Previously Untreated Non-M3 Acute Myeloid Leukemia (SWOG S0703): Report On the Poor Risk Patients

Increasing age and worsening performance status (PS) are associated with low complete remission (CR) rates and high early death rates in patients (pts) with acute myeloid leukemia (AML). Data from 4 SWOG trials show that in patients ≥70 and PS of ≥ 2, the CR rate with standard chemotherapy is 29% and 30-day death rate 48%. Preliminary data suggest that a regimen combining azacitidine (AZA) and gemtuzumab ozogamicin (GO) has significant activity and low toxicity in this group of patients. The current trial was designed to test this regimen in a larger group of patients in a cooperative group setting.

Newly diagnosed pts, ≥60 years of age, with de novo or secondary non-M3 AML were treated as follows: Induction: Hydroxyurea 1500 mg twice daily till WBC <10,000/mcL, followed by azacitidine 75 mg/m2/day s/cu or iv days 1–7, gemtuzumab ozogamicin 3mg/m2 D8. If D14 marrow showed residual disease, induction treatment was repeated. Those achieving CR received one consolidation treatment which was identical to the induction treatment. This was followed by 4 cycles of azacitidine 75/m2/day, D1–7, given every 4 weeks. Subsequent management was left to the treating physicians. Patients were prospectively entered into good risk (age 60–69 or PS 0–1) and poor risk (age ≥70 and PS 2 or 3) cohorts. Based on our previous experience, we concluded that the regimen would be worth further study if CR+CRi was ≥ 30% and a 30 day survival was ≥ 70%. Promoter and global methylation studies were performed at defined time points.

Data on 83 good risk pts were presented at ASCO 2012. The results presented here are from the poor risk cohort. A total of 54 poor risk pts were treated. Median age was 76 (70.3–87) and 33 were males. Five pts had pre-existing MDS. Of the 54 evaluable pts, 19 (35%) achieved a CR or CRi. One additional pt achieved a CR with continued AZA therapy after being removed from the study for persistent disease on D28. Median progression free survival is 7 mo and median overall survival 6 months. There were 31 grade 3 or 4 toxicities. Seven (14 %) pts died early, with a 30 day survival of 86%. An estimated 30% of the pts (in good risk and poor risk groups) were able to receive their induction therapy in the outpatient setting.

The combination of hydroxyurea, azacitidine and GO is associated with lower induction mortality, can be given in the outpatient setting and results in a CR rate better than that seen in poor risk pts with AML treated with standard chemotherapy. These results are sufficiently encouraging to warrant further studies with this approach.

Clinical Trials.govIdentifier: NCT00658814.

Nand:Celgene: Research Funding.