Clinical Trial Results Reveal Safety Issues With Nplate In Lower-Risk MDS Patients (ASH 2011)
Results of a recent clinical trial show that lower-risk myelodysplastic syndromes patients treated with Nplate have fewer bleeding problems, require fewer platelet transfusions, and are more likely to have increased platelet counts than patients treated with a placebo.
However, the trial investigators also found transient increases in immature blood cell counts and a higher risk for progression to acute myeloid leukemia in patients treated with Nplate.
They therefore decided to discontinue treatment with Nplate.
The results of the trial also have been reflected in important warnings that have been added to Nplate’s official prescribing information. The changes make clear that Nplate is not approved for use in patients with myelodysplastic syndromes (MDS), and that its use in patients with MDS involves substantial risks.
Dr. Aristoteles Giagounidis of the St. Johannes Hospital in Duisburg, Germany, presented the clinical trial results at the American Society of Hematology (ASH) 2011 meeting in December.
Platelets are a type of blood cell that is needed for the blood to clot. People with low platelet counts may have difficulty with blood clotting after injury and, as a result, may experience excessive bleeding.
Nplate (romiplostim) is a protein that increases platelet production. It is approved as a treatment for people who, for unknown reasons, chronically have abnormally low platelet counts. This condition is known as idiopathic thrombocytopenic purpura (ITP) or chronic immune thrombocytopenia.
According to the study authors, low platelet counts are seen in about 50 percent of lower-risk myelodysplastic syndromes patients. In addition, low platelet counts in lower-risk MDS patients may be associated with poor prognosis (see related Beacon news).
Previous smaller-scale studies have shown that Nplate may be effective in increasing lower-risk MDS patients’ platelet counts (see related Beacon news).
In the current study, researchers investigated Nplate’s efficacy and safety in a larger group of lower-risk MDS patients.
The study included 250 lower-risk MDS patients from Europe, Australia, and the United States. The median patient age was 70 years.
Patients were randomly assigned to receive either 750 mg Nplate (167 patients) or a placebo (83 patients) for 26 weeks.
The researchers found that patients who received Nplate experienced fewer significant bleeding events (1.47) than patients who received the placebo (1.94).
Additionally, patients receiving Nplate needed fewer platelet transfusions than patients who received the placebo.
Platelet counts were also more likely to improve in patients receiving Nplate (37 percent of patients) than in those receiving the placebo (4 percent).
However, the researchers also found that increases in immature blood cells, known as “blasts,” occurred more frequently among patients who received Nplate (15 percent) than patients who received the placebo (4 percent). They pointed out that the increases generally resolved once treatment with Nplate was discontinued.
Additionally, after 58 weeks, more patients who received Nplate (6 percent) had progressed to acute myeloid leukemia than patients who received the placebo (2 percent).
Overall survival after one year was similar between the patient groups (80 percent in the Nplate group and 78 percent in the placebo group).
Forty percent of patients treated with Nplate experienced severe side effects compared to 27 percent of patients treated with the placebo. The most common severe side effects associated with Nplate treatment included diarrhea, difficulty breathing, and bleeding in the brain.
Due to the results of this trial, the prescribing information for Nplate that is approved by the U.S. Food and Drug Administration now includes several important statements related to the drug’s use in patients with MDS.
The “Limitations of Use” section of the prescribing information states that the drug is not approved for the treatment of low platelet counts due to myelodysplastic syndromes.
In addition, the “Warnings and Precautions” section states that Nplate, when used to treat patients with MDS, “increases the risk of progression to acute myelogenous leukemia [AML].”
- Nplate May Be Safe For Lower-Risk MDS Patients (ASH 2012)
- Nplate May Increase Platelet Count During Vidaza Treatment For Myelodysplastic Syndromes
- Nplate Effective For Increasing Platelet Counts In Myelodysplastic Syndromes Patients (ASCO 2009)
- Researchers Determine Nplate Starting Dose For The Treatment Of Low Platelet Levels In MDS
- Nplate May Be Effective In Treating Thrombocytopenia In Myelodysplastic Syndromes Patients