Azacitidine Has Limited Activity in Patients with MDS and AML

The multicenter, randomized AZA-001 trial demonstrated that azacitidine (AZA) significantly improved overall survival in patients with intermediate-2/high risk MDS (including patients with AML < 30 % marrow blasts), compared with conventional care regimens, including supportive care, low dose cytarabine (LDAC) and intensive chemotherapy (Lancet Oncol 2009;10:223–32). Recent data has suggested that AZA may have limited efficacy in the “real life” situation (Hematol Oncol 2011Mar8; Epub ahead of print). This retrospective analysis evaluates the responses and outcomes of patients with MDS and AML < 30% marrow blasts who received AZA at the Princess Margaret Hospital.

Between July 2009 and July 2011, 87 patients received AZA at the Princess Margaret Hospital. This analysis is restricted to patients with MDS and AML < 30% marrow blasts (n = 60), excluding AML with > 30% blasts (n = 6), MDS/myeloproliferative neoplasm (n = 1), and patients previously treated with intensive chemotherapy and/or alloSCT within the last 5 years (n = 20). Azacitidine was planned to be administered subcutaneously at the dose-schedule of 75 mg/m²/d for 6 days every 28 days. However, 8 patients received subsequent cycles of AZA in local centers at the dose schedule of 75 mg/m²/d for 5 days, 2 days off, followed by 75 mg/m²/d for 2 days (AZA 5-2-2).

Median age was 73 (range, 43 to 87), and 63% were male. Twenty-three patients (38%) had secondary or therapy-related MDS or AML. Two patients had received a prior organ transplant (heart and liver). Forty-two patients (70%) had MDS (7 RCMD, 10 RAEB-1, 17 RAEB-2, 3 CMML-1, 5 CMML-2). Cytogenetic risk (by IPSS criteria) was good in 19 (32%), intermediate in 6 (10%), and poor in 33 (55%) patients, respectively. Karyotype analysis failed in 2 patients (3%). IPSS was intermediate-1 in 4 (7%), intermediate-2 in 32 (53%), and high in 24 (40%) of the patients. Median baseline hemoglobin level, absolute neutrophil count and platelet count were 90.5 g/L, 0.9 × 10⁹/L, and 44.5 × 10⁹/L, respectively. Median prior therapies was 0 (range, 0–2) with 5, 3, 1, and 1 patients having previously received erythropoiesis-stimulating agent, hydroxyurea, LDAC, and decitabine, respectively.

The median number of AZA cycles administered was 5.5 (range, 0–19). The best response was CR in 4 (7%), marrow CR in 8 (13%), and hematologic improvements in platelets, neutrophils, and erythroid in 15 (25%), 9 (15%), and 5 (8%) patients, respectively. Fifteen patients remain on treatment. Treatment discontinuation was mostly due to disease progression, lack of response, and/or intercurrent illness/infection, with 7 (12%) patients stopping therapy to proceed to an alloSCT. Twenty patients have died. Median overall survival was 36.7 weeks (range, 4.4 weeks-86.6+ weeks).

Azacitidine has limited efficacy in this group of patients. Optimal therapy for this patient population still needs to be determined.

Yee:Celgene: Honoraria. Schuh:Celgene: Honoraria.