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
Authors: Nand Sucha , Othus Megan , Godwin John E. , Willman Cheryl L , Norwood Thomas , Erba Harry Paul , Howard Dianna , Coutre Steven E. , Appelbaum Frederick R. 
Published: October 2019

Abstract
Abstract 3584

Background:
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.

Methods:
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.

Results:
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.

Conclusions:
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.

Disclosures:
Nand: Celgene: Research Funding.