Hematological Malignancies Hillary Prescott, PharmD, BCOP,1
Treatment Options for Myelodysplastic Syndromes Elias Jabbour, MD,2
Jeffrey Bryan, PharmD1
and Hagop Kantarjian, MD3 1. Clinical Pharmacy Specialist; 2. Assistant Professor; 3. Chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center
Abstract
Myelodysplastic syndromes (MDS) are a group of heterogeneous hematopoietic stem cell disorders characterized by peripheral blood cytopenias and a risk of transformation to acute myeloid leukaemia. Until recently, treatment of MDS predominately consisted of supportive care measures. However, three agents for the treatment of MDS have recently been approved: lenalidomide, decitabine, and azacitidine. These agents have dramatically improved the outcomes for patients with MDS. To date, azacitidine is the only agent that has demonstrated a survival advantage when compared with conventional care. Novel agents and combination regimens including lenalidomide, decitabine and azacitidine are being explored in an effort to further improve patient outcomes.
Keywords Myelodysplastic syndromes, MDS, azacitidine, decitabine, lenalidomide, hypomethlyating agents, supportive care, immunosuppressive therapy
Disclosure: The authors have no conflicts of interest to declare. Received: March 5, 2010 Accepted: September 26, 2010 Citation: US Oncology & Hematology, 2011;7(2):143–5 Correspondence: Elias Jabbour, MD, Department of Leukemia, Unit 428, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. E:
ejabbour@mdanderson.org
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders that impair normal hematopoiesis, resulting in a variable number of cytopenias and a potential to evolve into acute myeloid leukaemia (AML).1
70 years, MDS typically affects the elderly.1,2
With a median age at diagnosis around Hence, there is much
morbidity and mortality associated with this patient population, as patients frequently suffer from complications due to cytopenias as well as other comorbidities. The two systems used for classifying MDS are the French American and British (FAB) criteria and the more recently revised World Health Organization (WHO) classification system. A third system, the International Prognostic Scoring System (IPSS), can predict survival based on percentage of bone marrow blasts, karyotype and number of peripheral blood cytopenias3
and is the most widely used prognostic tool for assisting with treatment decisions.
For many years, supportive care with blood products (red blood cell [RBC] and platelet transfusions), hematopoietic growth factors and antibiotics remained the only treatment modality for MDS patients, until the development of three novel agents that may alter the natural history of this disease. Within the past decade, the US Food and Drug Administration (FDA) has approved an immunomodulatory agent, lenalidomide (Revlimid™, Celgene) and two hypomethylating agents, decitabine (Dacogen™, Eisai, Inc.) and azacitidine (Vidaza™, Celgene) for the treatment of patients with MDS. In simple practice, therapy is tailored to IPSS score with an emphasis on supportive care therapies or lenalidomide for lower-risk patients (IPSS low or intermediate [int]-1) and more intensive therapies such as conventional chemotherapy, allogeneic hematopoietic stem cell transplant (HST) and clinical trials,
© TOUCH BRIEFINGS 2011
as well as hypomethylating agents, for patients with higher-risk disease (IPSS int-2 or high) or lower-risk patients with progressive disease.3
Treatment of Lower-risk Myelodysplastic Syndromes Supportive Care
Initial clinical management of lower-risk MDS patients with symptomatic anemia includes the use of erythropoiesis stimulating agents (ESAs), such as epoetin alpha (Epogen™, Amgen; Procrit™, Ortho Biotech) or darbepoetin alpha (Aranesp™, Amgen). ESAs have been shown to reduce RBC transfusion needs in MDS patients and when given with granulocyte colony-stimulating factor (G-CSF), ESAs have been shown to confer a survival advantage.4
The likelihood of response to ESAs has been
correlated with RBC transfusion needs and serum erythropoietin (EPO) levels. Patients with low transfusion requirements (<two units packed red blood cells [pRBC] per month) and with baseline serum EPO level ≤500 mU/ml are predicted to have a good response to ESAs and G-CSF, whereas patients with higher transfusion needs (≥two units pRBC per month) and serum EPO levels >500 mU/ml are least likely to respond to ESAs.5,6
Demonstrated in a recent prospective, randomised study by the Eastern Cooperative Oncology Group (ECOG), patients with low-risk MDS and low serum EPO levels experienced higher erythroid response rates when given ESAs with or without G-CSF compared with patients with high-risk disease.7
Immunosuppressive Therapy
A subset of MDS patients with bone marrow failure responds to immunosuppressive therapy (IST), which suggests that an immune-
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