Decitabine Enhances CAG Outcomes in Older Leukemia Patients

The combination of decitabine (DAC) and cytarabine, acclarithromycin, and granulocyte colony-stimulating factor (CAG) vs CAG alone showed greater efficacy among older patients with acute myeloid leukemia (AML), with total response rate and complete response (CR) rate superior but partial response (PR) rate comparable, according to the results from a meta-analysis of 13 independent studies.

Publishing their results in Leukemia Research Reports,¹ the study authors explained that low survival rates and poor prognoses predominate disease outcomes among older patients with AML, who often also have suboptimal chemotherapy outcomes. CAG has shown positive results in patients with relapsed or refractory disease, but its impact among older patients remains limited, and robust data are needed.

“In terms of pharmacological analysis, DAC can make up for the deficiency of CAG in inducing differentiation and apoptosis of cancer cells,” they wrote.

For the period of inception through November 2022, they searched Pubmed, Chinese National Knowledge Infrastructure, Wanfang Database, and VIP database using the terms Decitabine, DAC, CAG, elder, acute myelogenous leukemia, AML, and pregenous chemotherapy. Included studies could not be duplicated literature or a review, case report, systematic analysis, or retrospective analysis. A P value of less than .05 was considered statistically significant for sensitivity.

Overall, 13 studies were included, with 11 involving various lengths of investigations for treatment regiments of CAG plus DAC 15 mg/m² or 20 mg/m². One each involved half-dose CAG plus DAC 10 mg/m² and low-dose CAG plus DAC 10 mg/m²/d. All had confirmed high methodological quality. There were 576 patients who received combination therapy and 557, monotherapy.

Looking at CR rate, PR rate, and overall rate, respectively, the following results were seen:

• DAC plus CAG: 48.26%, 32.29%, and 80.56%
• CAG alone: 32.68%, 28.01%, and 60.68%

There were also higher rates of several adverse effects in the combined treatment vs monotherapy cohort:

• Gastrointestinal reactions: 32.81% vs 23.52%
• Infection: 30.03% vs 16.88%
• Fever: 16.84% vs 6.28%
• Liver and kidney injury: 13.02% vs 12.93%
• Myelosuppression: 9.90% vs 9.52%
• Hematological adverse reactions: 17.36% vs 23.16%
• Alopecia: 1.56% vs 2.33%
• Heart injury: 1.04% vs 1.44%

The chance of a CR was higher in the DAC-plus-CAG group (OR, 1.99; 95% CI, 1.29-7.42; Z = 5.50; P < .001), but the chance of PR was not considered statistically significant (OR, 1.24; 95% CI, 0.95-1.61; Z = 1.59; P = .11). Overall, the combined result was an OR of 0.27 (95% CI, 0.20-0.37), and the total effective rate of the DAC-plus-CAG group was higher vs the CAG-alone group (Z = 8.71; P < .001).

The chance of infection was also higher in the DAC-plus-CAG group vs the CAG-alone group (OR, 2.67; 95% CI, 1.56-4.59; Z = 3.56; P = .0004), as was chance of fever (OR, 3.74; 95% CI, 2.41-5.82; Z = 5.86; P < .001). Combined ORs for both groups were 2.67 for infection and 1.99 for fever. The remaining AE results were not considered statistically significant between the 2 groups:

• Hematological adverse reactions (P = .14)
• Gastrointestinal reactions (P = .05)
• Alopecia (P = .39)
• Heart injury (P = 0.55)
• Liver and kidney injury (P = .74)
• Myelosuppression (P = .82)

The authors highlighted there was potential minimal publication bias and satisfactory symmetry, and they explained the combination regimen is so effective because DAC has several mechanisms through which it exerts antileukemic effects, including antiproliferative and proapoptotic pathways.²

“It is suggested that DAC combined with CAG regimen has certain effects in the clinical treatment of elderly AML patients,” the authors concluded. “However, attention should be paid to the occurrence of adverse reactions, especially the occurrence of lung infection and fever. Proactive implementation of management strategies is essential to maintain therapeutic efficacy.”

They recommend preemptive management of adverse reactions, due to the higher rates they saw with the combination regimen, along with larger-scale, high-quality randomized controlled studies for confirmation of their findings.

Limitations on these results are the small sample size and the short treatment durations of some of the studies.

References

1. He Y, Zhang L, Liu M, Zhang F, Gao H. Meta-analysis of clinical efficacy and safety of decitabine combined with CAG regimen in the treatment of acute myeloid leukemia in the elderly. Leuk Res Rep. 2025;25:100559. doi:10.1016/j.lrr.2025.100559
2. Meier R, Greve G, Zimmer, D, et al. The antileukemic activity of decitabine upon PML/RARA-negative AML blasts is supported by all-trans retinoic acid: in vitro and in vivo evidence for cooperation. Blood Cancer J. 2022;12(8):122. doi:10.1038/s41408-022-00715-4