Clinical Results of Hypomethylating Agents in AML Treatment
Abstract
:1. Introduction
2. DNA Hypomethylating Agents
3. Azacitidine and AML
4. Decitabine and AML
5. Azacitidine and Decitabine in 10-Day Schedules
Azacitidine (7 Days 75 mg/m2 SC; Every 4 Weeks) | ||||
---|---|---|---|---|
Study | Competitors | CR (%) | Median OS | 1/2-Year OS |
Post hoc analysis CALGB 9221 (AML 20%–30% blasts) [11] | AZA (n = 27) vs. Observation (n = 12) | 7% vs. 0% | 19.3 months vs. NA; Combining CALGB 8421, 8921, 9221: 12.9 months (n = 25; p = NA) | NA |
Post hoc analysis AZA001 study (AML 20%–30% blasts) [12] | Aza (n = 55) vs. CCR (n = 58) (BSC = 27/LDAC = 20/IC = 11) | 18% vs. 16% | 24.5 months vs. 16 months (p = 0.005) | 50% vs. 16% (p = 0.001) (2-year OS) |
AML001 study (AML >30% blasts) [13] | Aza (n = 241) vs. CCR (n = 247) (BSC = 45/LDAC = 158/IC = 44) | 20% vs. 22% | 10.4 months vs. 6.5 months (p = 0.08). Analysis censored for subsequent Tx: 12.1 months vs. 6.9 months (p = 0.01) | 46.5% vs. 34.2% (p = NA) (1-year OS) |
Decitabine (5 Days 20 mg/m2 IV; Every 4 Weeks) | ||||
DACO-016 (AML >20% blasts; only intermediate and poor risk) [19] | Decit (n = 242) vs. TC (n = 243) (BSC = 28/LDAC = 215) | 15.7% vs. 7.4% | 7.7 months vs. 5.0 months (p = 0.11). Analysis censored for subsequent Tx: 8.5 months vs. 5.3 months (p = 0.04). Unplanned analysis after 446 deaths: 7.7 months vs. 5.0 months (p = 0.04) | NA |
Azacitidine | |||
---|---|---|---|
Study | Dosing | CR (%) | Median OS |
Post hoc analysis AML001 study (phase 3) (AML 20%–30% blasts) [12] | Aza (n = 55) 7 days 75 mg/m2 SC; every 4 weeks | 18% | 24.5 months |
AML001 study (phase 3) (AML >30% blasts) [13] | Aza (n = 241) 7 days 75 mg/m2 SC; every 4 weeks | 20% | 10.4 months |
United States Leukemia Intergroup Trial E1905 (phase 2) [20] | Aza (n = 74) 10 days 50 mg/m2 SC; every 4 weeks | 12% | 18 months |
Decitabine | |||
German phase 2 study [14] | Decit (n = 227) 3 days (135 mg/m2 total) | 13% | 5.5 months |
DACO-016 (phase 3) (AML >20% blasts; only intermediate and poor risk) [19] | Decit (n = 242) 5 days 20 mg/m2 | 15.7% | 7.7 months |
Ohio State University experience (phase 2) [16] | Decit (n = 53) 10 days 20 mg/m2 | 47% | 12.7 months |
Cornell University experience (report of retrospective analysis) [17] | Decit (n = 52) 10 days 20 mg/m2 | 40% (after excluding 6 patients who received prior azanucleotide CR = 46%) | 10.5 months |
6. Hypomethylating Agents as Maintenance Therapy
7. DNA Hypomethylating Agent Therapy as a Bridging Strategy to AlloHCT
8. Use of Hypomethylating Agents after AlloHCT
9. Treatment of Older AML Patients
10. Conclusions
Author Contributions
Conflicts of Interest
References
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Cruijsen, M.; Lübbert, M.; Wijermans, P.; Huls, G. Clinical Results of Hypomethylating Agents in AML Treatment. J. Clin. Med. 2015, 4, 1-17. https://doi.org/10.3390/jcm4010001
Cruijsen M, Lübbert M, Wijermans P, Huls G. Clinical Results of Hypomethylating Agents in AML Treatment. Journal of Clinical Medicine. 2015; 4(1):1-17. https://doi.org/10.3390/jcm4010001
Chicago/Turabian StyleCruijsen, Marjan, Michael Lübbert, Pierre Wijermans, and Gerwin Huls. 2015. "Clinical Results of Hypomethylating Agents in AML Treatment" Journal of Clinical Medicine 4, no. 1: 1-17. https://doi.org/10.3390/jcm4010001