by Dr. C.H. Weaver M.D. 7/2020
On July 7, 2020, the Food and Drug Administration approved an oral combination of Dacogen (decitabine) and Inqovi (cedazuridine) for adult patients with myelodysplastic syndromes (MDS) including the following:
- previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and
- intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
This represents an important advance in treatment options for patients with MDS, especially during the COVID era, who previously needed to visit a health care facility to receive intravenous therapy. Both Dacogan and Inqovi can be taken orally.
About Myelodysplastic Syndromes (MDS)
MDS is a disease in which the cells in a person’s bone marrow are not functioning normally. The bone marrow (and circulating blood) contains early blood-forming cells called stem cells, which grow and mature into the 3 blood cell types: white blood cells, which protect the body from infection; red blood cells, which carry oxygen to the tissues; and platelets, which help the blood to clot. In the case of MDS, not enough normal blood cells are being produced and/or the blood cells die prematurely. This condition is sometimes referred to as a pre-leukemia or “smoldering” leukemia because it often develops into acute myeloid leukemia (AML), an aggressive type of cancer. Some patients with MDS also have additional abnormalities, including genetic abnormalities of the blood cells, a high number of immature blood cells (called blasts) in the bone marrow, or decreasing numbers of red blood cells, white blood cells, or platelets. These individuals are at a higher risk for a more rapid progression to leukemia than are those who have more favorable cell features.
About Inqovi (cedazuridine)
Inqovi is an orally available synthetic nucleoside analog derived from tetrahydrouridine (THU) and cytidine deaminase inhibitor (CDAi), that can potentially be used to prevent the breakdown of cytidines. Upon oral administration, Inqovi binds to and inhibits CDA, an enzyme primarily found in the gastrointestinal (GI) tract and liver that catalyzes the deamination of cytidine and cytidine analogs. Given in combination with a cytidine, such as the antineoplastic hypomethylating agent decitabine, it specifically prevents its breakdown and increases its bioavailability and efficacy. This also allows for lower doses of decitabine, which results in a decreased decitabine-associated GI toxicity. Check for active clinical trials using this agent
Inqovi combined with Dacogen was investigated in two clinical trials in 213 adult patients with MDS or CMML demonstrating a complete response rate of 18% and a median duration of that response of 8.7 months with the lead patient in remission approaching 2 years. Among the 41 patients who were dependent on red blood cell and/or platelet transfusions at baseline, half became independent of transfusions.
Common side effects of Inqovi included fatigue, constipation, hemorrhage, muscle pain, mucositis (mouth sores), arthralgia (joint pain), nausea, and fever with low white blood cell count. Inqovi can cause fetal harm, and both male and female patients of reproductive age are advised to use effective contraception.