Azacitidine Has Limited Activity in Patients with MDS and AML
Authors: Yee Karen , Bansal Symron , Brandwein Joseph , Minden Mark D. , Schimmer Aaron , Gupta Vikas , Dharman Arsenia , Cserti-Gazdewich Christine , Schuh Andre 
Published: October 2019

Abstract
Abstract 5057

Background:
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.

Methods:
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).

Results:
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).

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

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