Phase II study of decitabine and gemtuzumab ozogamicin (GO) in acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

Abstract

6566 Background: Antileukemic activity of GO correlates with expression of Syk, a tumor suppressor, in AML cells. Hypomethylating agents increase expression of Syk in AML cells. A phase II study of 5-azacitidine with GO in elderly untreated AML patients (pts) showed remission rate of 70%. We are investigating the efficacy and safety of the combination of GO with decitabine in AML and MDS. Methods: Induction comprises of decitabine 20 mg/m2 intravenously (IV) daily for 5 days and GO 3 mg/m2 IV X 1 on day 5. Initially an additional GO dose was allowed if pt had circulating blasts on day 14, but was revised to add 5 days of decitabine instead of GO on day 15 ± 2, if day 14 bone marrow shows > 5% blasts. Subsequent therapy allows for 5 additional cycles of decitabine and GO every 4-6 weeks. Pts with responses can continue with decitabine x 5 days every 4-6 weeks for 2 years. This report is limited to the previously untreated patients with AML or MDS. Results: We report on the 56 pts (AML = 37, MDS = 19) with previously untreated AML or MDS. The median age was 70 years (range, 42-87), 36 (58%) were male. Twenty-six (46%) pts were treated on the original schedule and 30 (54%) on the revised schedule. Responses were seen in 26 (46%) pts (10/26 [38%] in original schedule, 16/30 [53%] in revised schedule). Sixteen pts (29%) (6/26 [23%] in original schedule, 10/30 [33%] in revised schedule) achieved complete remission (CR) or CR without platelet recovery (CRp). Two pts had partial remission, 7 had clearance of marrow blasts and 1 had hematological improvement-hemoglobin. Toxicities were mostly related to infusion reactions with GO. Twelve pts had infections requiring hospitalization. Grade 3/4 nonhematologic toxicities include atrial flutter (1 pt) and 1 transient ischemic attack. There were 2 early deaths. Responding pts have continued therapy for a median day of 202 (range, 40-540). Conclusions: Decitabine plus GO is an active regimen in older pts with untreated AML or high-risk MDS, toxicities are minimal. The accrual in this study is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai