Decitabine therapy in AML patients with monosomal karyotype

Decitabine (DEC) therapy improved response rate and led to a longer Progression Free Survival (PFS) in older Acute Myeloid Leukemia (AML) patients with Monosomal Karyotype (MK) according to results of a sub-analysis of the phase III randomized DACO-016 study (NCT00260832), published in American Journal of Hematology by Agnieszka Wierzbowska [member of the AML Global Portal (AGP) European Steering Committee] from the Medical University of Lodz, Lodz, PL, and colleagues.¹

The phase III randomized DACO-016 study compared DEC versus Treatment Choice (TC) in older patients with newly diagnosed AML. Findings of this study demonstrated that DEC led to an improved complete response rate and a longer Overall Survival (OS) compared to TC in older newly diagnosed AML.² Wierzbowska et al., conducted a post-hoc analysis whose main objectives were to determine the effects of DEC versus TC on outcomes of AML patients with MK+ disease, and to compare versus MK− AML with other unfavorable karyotypes.¹

In this DACO-016 study, 485 newly diagnosed AML patients were randomly assigned to either receive decitabine (20 mg/m² /day for 5 consecutive days every 4 weeks) or TC (best supportive care or cytarabine 20 mg/m²/day for 10 days every 4 weeks).  Of these, patients with MK+ (n = 64 [DEC, n = 33, TC, n = 31]) and MK- with poor cytogenetics (n = 99 [DEC, n = 49, TC, n = 50) were identified and included in this post-hoc analysis.

Key findings:

• MK+ group
  • Overall Response Rate (ORR) in the DEC and TC arm: 36% (12/33) vs 3% (1/31), P = 0.0013
  • Median PFS in the DEC and TC arm: 2.6 vs 1.3 months, HR = 0.53 (95% CI, 0.31 – 0.90), P = 0.0181
  • Median OS in the DEC and TC arm: 6.3 vs 2.6 months, HR = 0.67 (95% CI, 0.39 – 1.15), P = 0.141
• MK- poor-risk cytogenetics group
  • ORR in the DEC and TC arm: 18% (10/49) vs 12% (6/50), P = 0.287
  • Median PFS in the DEC and TC arm: 2.4 vs 2.2 months, HR = 1.13 (95% CI, 0.74 – 1.72], P = 0.576
  • Median OS in the DEC and TC arm: 5.0 vs 4.7 months, HR = 1.13 (95% CI, 0.72 – 1.70), P = 0.576
• In the TC arm, there was a trend for poorer OS in MK+ patients compared to patients who were MK-: 2.6 vs 4.7 months respectively, HR = 1.52 (95% CI, 0.91 – 2.54), P = 0.107
• In the DEC arm, median OS was similar between MK+ and MK- patients: 6.3 vs 5.0 months respectively, HR = 0.98 (95% CI, 0.60 – 1.58), P = 0.924

The authors concluded by highlighting that DEC “improved response rates and PFS compared with other standard therapies for patients who were ineligible for intensive chemotherapy, with a benefit of almost 4 months in median OS”.  Furthermore, "decitabine may overcome the extremely poor prognosis associated with MK, and may be a beneficial initial treatment in these patients".

Key limitations of this post-hoc study include the open-label design of the DACO-016 study, the post-hoc nature of the analysis, and the relatively small number of patients. The authors noted that the findings of this post-hoc analysis should be confirmed in large prospective studies.