Azacitidine Vs. Decitabine in Unfit Newly Diagnosed Acute Myeloid Leukemia Patients: Results from the Pethema Registry

Background:

Options to treat elderly patients with newly diagnosed AML include intensive, attenuated chemotherapy, hypomethylating agents (HMA) and supportive care (SC). HMA have proven their efficacy in DACO-016 (NCT00260832) and AML-001 (NCT01074047) clinical trials, with a median overall survival (OS) of 7.7 months (95%CI, 6.2 to 9.2) with decitabine (DEC) vs. 5.0 months (95%CI, 4.3 to 6.3) with therapy choice (TC), considered SC or low-dose Ara-C (LDAC). Median OS was 10.4 months with azacitidine (AZA) (95%CI, 8.0 to 12.7) vs. 6.5 months (95%CI, 5.0 to 8.6) with conventional care regimens (CCR), considered standard induction chemotherapy, LDAC or SC. However, there are few direct comparative data of AZA and DEC in the context of trials or real-life settings.

Aims:

Here, we compared clinical outcomes between AZA and DEC in AML patients not eligible for intensive chemotherapy in the epidemiologic PETHEMA registry.

Methods:

We included newly diagnosed AML patients treated with AZA (75 mg/m2/d IV or SC days 1–7) or DEC (20 mg/m2/d IV days 1–5) that were not eligible for intensive chemotherapy.

Responses were recorded using IWG 2003 criteria. Rates of Complete Response (CR), complete response with incomplete recovery (CRi) and OS were co-primary endpoints.

Results:

Between 2006 and 2019, 638 patients were included. 497 (78%) received AZA and 141 (22%) received DEC as per physician judgement.

Baseline characteristics were comparable in both groups (Table 1), except for bone marrow blasts count ≥ 30%, which was more frequent in DEC group (59.2% vs 77.1%, p<0.001).

The CR rate was 16.3% vs 20.6% (p = 0.23); composite CR (CR+CRi) was 18.5% vs 22% (p = 0.35), and the overall response rate (ORR, partial remission (PR) plus CR+CRi) was 29.2% vs 34.8% (p=0.20); for AZA vs DEC, respectively.

A significantly higher ORR to AZA was associated with ECOG <2 (33.9% vs. 12.4% in patients with ECOG ≥2, OR 0.22, 95% CI 0.10 – 0.49, p=0.000), de novo AML (35.3% vs. 21.9% in secondary AML; OR 0.38, 95% CI 0.20 – 0.71, p=0.002) and estimated glomerular filtrate rate ≥ 45 mL/min/1.73m² (30.4% vs. 9.3% in patients with estimated glomerular filtrate rate ≥ 45 mL/min/1.73m²; OR 0.15, 95% CI 0.034 – 0.67, p=0.013); while bone marrow blast count < 50% was the only factor influencing ORR to DEC (43.7% vs. 25% in ≥ 50% bone marrow blasts, p=0.029).

With a median follow up of 12 months, median OS was 10.0 (95% CI 8.7 – 11.2) vs 8.0 (5.7– 10.2) months for AZA vs DEC, respectively (p = 0.46) (Figure 1). Median OS was 21 (17.8 – 24.1) vs 16 (12.6 – 19.3) vs 6 months (5.0 – 7.0) for patients who achieved CR/CRi vs PR vs no response (p<0.001) (Figure 2).

Additional subgroup analyses by baseline characteristics performed to compare AZA vs DEC revealed that patients ≥ 80 years did benefit for treatment with AZA, median OS of 8 vs. 4 m (p=0.042), as well as patients with WBC ≥ 10 x10⁹/L (8 vs. 5 m, p=0.036), platelet count <20 x10⁹/L (8 vs. 4 m, p=0.021) and those with estimated glomerular filtrate rate ≥ 45 mL/min/1.73m² (10 vs. 5m, p=0.033).

Conclusions:

This is a large retrospective comparison with long-term follow-up of clinical outcomes associated with AZA and DEC treatment for patients with AML patients not eligible for intensive chemotherapy. There were no significant differences in ORR, CR/CRi or OS between AZA and DEC. However, patients with WBC ≥ 10 x10⁹/L, platelet count <20 x10⁹/L and estimated glomerular filtrate rate ≥ 45 mL/min/1.73m² could benefit from AZA in terms of OS.