[ Visit Client Website ]

Before you can access ASH's online program, you must agree to the following:
  • Abstracts submitted to the ASH Annual Meeting are considered embargoed from the time of submission.
  • The media, companies and institutions issuing press releases, and others are required to abide by the embargo policies governing the Society’s annual meeting. Read ASH’s embargo policy for more information.
-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session .

44 Maintenance Therapy with Decitabine in Younger Adults with Acute Myeloid Leukemia (AML) in First Remission: A Phase II Cancer and Leukemia Group B Study (CALGB 10503, Alliance)

Program: Oral and Poster Abstracts
Type: Oral
Session: 615. Acute Myeloid Leukemia - Therapy, excluding Transplantation: Novel Therapies
Sunday, December 9, 2012: 12:15 PM
A101, Level 1, Building A (Georgia World Congress Center)

William Blum, MD1, Ben Sanford2*, Rebecca B Klisovic, MD1, Daniel J. DeAngelo, MD, PhD3*, Geoffrey Uy, MD4, Bayard L. Powell, MD5, Wendy Stock, MD6, Maria R. Baer, M.D.7, Jonathan E. Kolitz, MD8, Meir Wetzler, MD9, Eva Hoke2*, Clara D. Bloomfield, MD10*, Susan Geyer, PhD11,12*, Guido Marcucci, MD13,14, Richard M. Stone, MD15 and Richard A. Larson, MD16

1Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH
2Alliance for Clinical Trials in Oncology Statistics and Data Center, Duke University Medical Center, Durham, NC
3Dana-Farber Cancer Institute, Boston, MA
4Washington University, Saint Louis, MO
5Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC
6Department of Medicine, The University of Chicago, Chicago, IL
7University of Maryland Greenebaum Cancer Center, Baltimore, MD
8Department of Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY
9Roswell Park Cancer Institute, Buffalo, NY
10Division of Hematology, Department of Internal Medicine, The Ohio State University and The Ohio State University Comprehensive Cancer Center, Columbus, OH
11Hematology and Oncology, The Ohio State University-James Cancer Center, Columbus, OH
12Alliance for Clinical Trials in Oncology Statistics and Data Center, The Ohio State University, Columbus, OH
13The Ohio State University Comprehensive Cancer Center, Columbus, OH
14Department of Molecular Virology, Immunology and Medical Genetics, Division of Human Cancer Genetics, The Ohio State University and The Ohio State University Comprehensive Cancer Center
15Medical Oncology, Dana-Farber Cancer Institute & HMS, Boston, MA
16Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL

CALGB (now part of the Alliance for Clinical Trials in Oncology) performed a non-randomized phase II study testing one year (yr) of investigational maintenance therapy with decitabine for newly diagnosed adult AML patients (pts) <60 yrs of age (CALGB 10503, Alliance). The study included induction followed by molecular and cytogenetic risk-adapted consolidation identical to that given in the prior CALGB study for younger AML pts (19808). Induction used daunorubicin 90 mg/m2 for 3 days, etoposide 100 mg/m2 for 3 days, and cytarabine 100 mg/m2 for 7 days (3+3+7). Reinduction (2+2+5) was given for residual disease on day 14. Favorable risk pts [defined here as t(8;21), inv(16), or t(16;16)] in complete remission (CR) received 3 cycles of high dose cytarabine (HiDAC); all other pts received two-step consolidation with chemo-mobilization and autologous transplantation (autoHCT) if eligible, or HiDAC-based consolidation if not. However, removal from study for alloHCT in 1st CR, instead of the two-step autoHCT, was permitted for non-favorable risk pts. Maintenance decitabine began as soon as possible after recovery from consolidation; pts had to have CR with neutrophils >1 x 109/L, platelets >75 x 109/L, and be within 90 days after day 1 of the final consolidation. Decitabine 20mg/m2 was given IV over 1 hour for 4-5 days, every 6 weeks, for 8 cycles. 546 pts enrolled with a median age of 48 yrs (range, 17-60) and median presenting  white blood count (WBC) of 12.6 x 109/L (range, 0.3-380 x 109/L). 75% achieved CR (412/546). Reasons for CR pts not receiving maintenance were mainly early relapse, alloHCT in 1st CR, inadequate count recovery, and patient refusal (Blum et al. ASH 2011). 33% of CR pts (134/412) received investigational maintenance. Of these, 46 (34%) were favorable risk; among the remaining 88 pts, 73 were consolidated with autoHCT, and 15 received HiDAC-based consolidation. The median time from initial study registration to initiation of maintenance therapy was 6.3 months. Pts receiving decitabine had a median age of 45 yrs (range, 18-60) and presenting WBC of 13.5 x 109/L (range, 0.4-221 x 109/L). Treatment with decitabine maintenance was feasible and reasonably well tolerated; the primary toxicity was myelosuppression. Preplanned dose reduction criteria for neutropenia were met after the first 20 pts had been treated. After this early timepoint, all subsequent pts who had been consolidated with autoHCT received only 4 days of decitabine per cycle (HiDAC consolidated pts continued to receive 5 days per cycle). The median number of cycles of decitabine received was 7 (range, 1-8); 46% of pts (62/134) received all 8 cycles, and 75% completed at least 4 cycles. Reasons for discontinuation of decitabine before completing 8 cycles included relapse (28%, 38/134), pt refusal (13%), adverse events (4%), and others. In this selected cohort of pts who received post-CR maintenance with decitabine, 1-yr and 3-yr overall survival (OS) were 96% and 66%; 1-yr and 3-yr disease-free survival (DFS) were 80% and 53%. 1-yr “failure-free survival” calculated from the time of registration to decitabine was 68% (70% for favorable risk, 68% for others). These results are similar to the outcomes for comparable pts enrolled on our prior CALGB study 19808 who received identical chemotherapy for induction and consolidation and then were randomized to observation or maintenance with interleukin-2 (3-yr OS 61% and 68%, 3-yr DFS 45% and 56%, for observation and IL-2 respectively). Post-consolidation maintenance with decitabine appears to provide only modest, if any, benefit overall. Correlative studies for CALGB 10503 are ongoing, including investigations into the impact of decitabine in unique molecular and cytogenetic subsets of disease, the prognostic/predictive value of aberrant methylation and other molecular markers, and assessment of minimal residual disease. Supported by CA33601 and CA128377.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH