PB2095 OUTCOME AFTER AZACITITINE TREATMENT IN PATIENTS WITH HIGH‐RISK MYEOLODYSPLASTIC SYNDROME, CHRONIC MYELOMONOCYTIC LEUKEMIA TYPE 2 AND ACUTE MYELOID LEUKEMIA–A SINGLE CENTER EXPERIENCE
Authors: Varbanova V. , Nicolov I. , Nedeva A. , Petkova N. , Kindekov I. , Kuyumdzhieva Y. , Anastasova‐Postadzhiyan M. , Kuncheva T. , Vikentieva E. , Popova D. , Mitev L. , Raynov J. 
Published: June 2019

Background:

Hypomethylating agents have become a standard therapy for intermediate‐2 and high‐risk International Prognostic Scoring System (IPSS) myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia with 10‐29% blasts (CMML‐2) and elderly patients with acute myeloid leukemia (AML).

Aims:

The aim of this preliminary study was to assess the efficacy and safety of azacitidine treatment in patients with MDS, CMML‐2 and AML by analyzing the therapeutic response, progression‐free survival (PFS) and overall survival (OS) for each group of treated patients.

Methods

Twenty‐six (69% male and 31% female) patients treated for the period April 2017 to October 2018 year in the Clinic of Hematology at Military Medical Academy, Sofia were included in the study. Azacitidine was administered subcutaneously at a dose of 75 mg/m2 for 7 days. Disease assessment was performed after the 3rd cycle, 6th cycle, and at progression.

Results:

The median age was 67.8 years (58‐80 years old). Thirteen had MDS intermediate‐2 IPSS MDS, 2 had high‐risk IPSS MDS, 2 had CMML‐2 and 9 were with AML. Azacitidine was administered as a first‐line therapy at 17 (65.4%), and as the second line in 9 (34.6%) patients. The median number of administered cycles was 6 (1‐16). Thirteen patients completed 6 cycles of azacitidine (8 patients with MDS, 2 with CMML‐2 and 4 with AML), 8 MDS patients have not complete due to progression, 3 (2 MDS, 1 AML) because of death and 2 patients (1 MDS, 1 AML) were ongoing but not reached 6 cycles. Erythroid response was achieved in 46.7% (n = 7, 4 MDS, 3 AML) after 3rd cycle and 66.7% (n = 10, 3 MDS, 1 CMML II, 2 AML) after 6th cycle. Platelet response was reached in 72.7% (n = 8, 6 MDS, 1 CMML II, 1 AML) after 3rd cycle and 40% (n = 2, 1 CMML II, 1 AML) after 6th cycle. Neutrophil response in 27.3% (n = 3, 2MDS, 1 AML) and 50%(n = 2, 2 MDS, 1 AML) after 3rd and 6th cycle. Bone marrow complete response was achieved in 4 patients (33.3%) (2 MDS, 1 AML and 1 CMML‐2), partial response in 3 (25.0%) (2 MDS and 1 AML), stable disease in 4 (33.3%) (2 MDS, 1 AML and 1 CMML‐2) and progression in 1 patient with AML (8.3%) after 6th cycle. For one patient there is missing data for bone marrow blast count. The median PFS in the MDS group was 7.9 months and in the AML group 9.7 months. None of the patients with CMML‐2 progressed at the end of the study. The median OS was 10.7 months in MDS group and 11.5 months in AML group. The most frequent grade≥ 3 adverse events was neutropenia 38.5 (n = 10), followed by anemia 15.4% (n = 4) and thrombocytopenia 11.5% (n = 3). The only found factor to correlate with shortened PFS and OS was IPSS high risk MDS (IPSS intermediate‐2 vs high ‐ PFS: 1.05 months vs 7.9 months, P = 0,01; OS: 1.4 months vs 12.39 months, P = 0.01).

Summary/Conclusion:

The therapy with azacitidine is an option for elderly patients with high‐risk MDS, AML and CMML II that provides PFS and OS for approximately one year irrespective of age or nosological subgroup. These are preliminary data and larger patient cohort and a longer follow‐up period are needed for clinical conclusions.