Transfusion Independence in Patients with Hematologic Disorders Receiving Azacitidine Who Are Enrolled in AVIDA, a Longitudinal Patient Registry
Authors: Grinblatt David L. , Narang Mohit , Malone James M. , Sweet David A. , Dunne Tim S. , Sullivan Kristen A. 
Published: April 2020

Abstract
Patients with myelodysplastic syndromes (MDS) or other hematologic disorders experience anemia and/or thrombocytopenia at some point during the course of their disease. Current management of these cytopenias includes frequent red blood cell (RBC) and platelet transfusions, and use of other supportive therapy (eg, erythropoietin). Dependence on transfusions can be coupled with diminished quality of life, poorer outcomes, and increased economic burden. Azacitidine, a hypomethylating agent approved in the US for the treatment of all 5 MDS subtypes, is associated with transfusion independence in patients enrolled in clinical trials (Silverman, et al. J Clin Oncol.2006;24:3895). The establishment of transfusion independence in patients receiving azacitidine in the non-clinical trial/community-based setting is not well characterized. AVIDA is a longitudinal, multicenter patient registry designed to prospectively collect data from community-based hematology clinics on the natural history and management of patients with MDS and other hematologic disorders, including acute myeloid leukemia, who are treated with azacitidine. Baseline demographics and disease characteristics were obtained at enrollment. Transfusion requirements and onset of RBC and platelet transfusion independence were recorded. Transfusion independence was defined as no transfusions for at least 56 days. The first day of the 56-day period with no transfusions was noted as the time at which patients first achieved transfusion independence. As of August 1, 2008, 220 (154 males, 66 females; mean age, 73.5 yrs) have been enrolled in AVIDA. At baseline, the majority of patients had primary MDS (183 patients; 83%), an ECOG performance status of 0 or 1 (164 patients; 75%), and an International Prognostic Scoring System (IPSS) risk classification of Low/Intermediate-1 (130 patients; 59%); 55 (25%) had a Intermediate-2/high IPSS risk and 35 (16%) had unknown IPSS risk. Median time from first MDS diagnosis until azacitidine treatment was 3 months (range, 0 to 149). A total of 732 cycles of azacitidine have been administered either by subcutaneous (46%) or intravenous (54%) infusion; 203 patients have received a median of 3 cycles (range, 1–15). The most common dose and schedule is 75 mg/m2 (82%) at 5 days on treatment (51%). Transfusion data are available for 136 patients who have received at least 2 cycles of azacitidine. Eighty-three of 136 (61%) patients had received at least 1 RBC transfusion during the 6 months prior to AVIDA. Of these patients, 33/83 (40%) achieved RBC transfusion independence; 23/33 (70%) first achieved RBC transfusion independence during the first 2 cycles of azacitidine therapy. Among those patients who had received a platelet transfusion 6 months prior to AVIDA, 13/22 (59%) achieved platelet transfusion independence; 11/13 (85%) first achieved platelet transfusion independence within the first 2 cycles. Azacitidine was generally well tolerated; the most common adverse events were anemia (18%), thrombocytopenia (14%), fatigue (13%), nausea (13%), constipation (12%), and neutropenia (10%). These data demonstrate that in the community-based setting, patients with MDS or other hematologic disorders can achieve transfusion independence within the first 2 cycles. The full benefit of achieving transfusion independence on quality of life and clinical outcomes will be elucidated as more patients are enrolled in AVIDA.