Lay Summary: I review some of the new drugs for myelodysplastic syndromes.
The main options available to MDS patients in the past were blood transfusions, antibiotics to prevent infection and blood cell growth factors, drugs designed to jumpstart blood cell production. Today, almost all patients still receive blood transfusions, but transfusions don’t provide long-term relief and repeated red blood cell transfusions often leave patients with iron-rich blood, a serious condition if left uncorrected. (Last year’s approval of Exjade® [deferasirox], the first oral drug designed to reduce iron overload, now makes the consequences of transfusion therapy less intrusive by replacing traditional infusion-based pump therapy.)
Donor stem cell transplant—currently the only curative treatment for MDS—may not be realistic for this older population.
Both Vidaza (5 azacytidine) and Dacogen (decitabine) are DNA methyltransferase inhibitors (DMTI) approved by the FDA for use in all French- American British (FAB) categories for MDS. In its pivotal trial, Vidaza was reported to produce a 60% response rate (RR) (7%CR, 16%PR 37% hematological improvement). Vidaza prolonged median time to progression (TTP) to MDS/acute myeloid leukemia (AML) from 12 months to 21 months (p=0.07). The response rates for Dacogen were 30% (9% CR, 8% PR, 13% HI). Median TTP was prolonged from 7.8 months to 12.1 months compared to supportive care (p=0.1). Higher response rates have been reported in a single institution trial using lower doses of Dacogen.
Silverman L, Demakos E, Peterson B, et L. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J. Clin. Oncol 2002; 10: 2241-2252.
Saba H, Rosenfeld C, Issa JP, et al. First Report of the Phase III North American Trial of Decitabine in Advanced Myelodysplastic Syndrome. American Society of Hematology Meeting. San Diego, Calif. 2004. Abstract #64.
Kantarjian H, O’Brien S, Giles F, et al.Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.American Society of Hematology Meeting. Atlanta, Georgia. 2005. Abstract #2522.