Researchers Determine Nplate Starting Dose For The Treatment Of Low Platelet Levels In MDS - The MDS Beacon

Researchers Determine Nplate Starting Dose For The Treatment Of Low Platelet Levels In MDS

No Comment By Emily Plummer
Published: Oct 26, 2010 11:20 am

A Phase 2 study of Nplate in myelodysplastic syndromes patients resulted in increased platelet levels in patients, independent of dosing schedule and route of administration. However, differences in duration of response and side effects led researchers to recommend under-the-skin injection of 750 μg once weekly as the Nplate starting dose schedule for myelodysplastic syndromes patients.

Low platelet levels (thrombocytopenia) are present in 40 percent to 65 percent of myelodysplastic syndromes (MDS) patients.  Low platelet levels are an inherent problem in many MDS patients and can also be caused by MDS treatments.  Low platelet levels are often linked to faster disease progression.

Platelet transfusion, the only available treatment for low platelet levels, is required in 35 percent of low-risk MDS patients. Platelet transfusion is expensive, and potential risks include allergic reaction, infection, lung injury, and alloimmunization, in which the patient gains immunity to the foreign cells and the treatment becomes ineffective.

Researchers are currently investigating the use of platelet growth factors for the treatment of low platelet counts in MDS. Platelet growth factors enhance the production of platelets.

“An effective platelet growth factor would be very important for patients with severe thrombocytopenia,” said Dr. Ronald Paquette from the Ronald Reagan University of California Los Angeles Medical Center.

According to Dr. Mikkael Sekeres, lead author on the study, increasing platelet levels with platelet growth factors will probably reduce some of the morbidity associated with MDS, such as bleeding events, but they will not delay transformation to acute myeloid leukemia.

Nplate (romiplostim) is a platelet growth factor that is currently approved for treatment of low platelet levels in patients with chronic immune thrombocytopenia.

Previous studies have shown that Nplate is effective in increasing platelet levels in MDS patients. The optimal dose was determined to be 750 μg.

In this study, researchers in the United States and Europe evaluated three different dosing schedules and routes of administration of Nplate in MDS patients with low platelet levels to determine the optimal Nplate dosing schedule.

The Phase 2 study involved 28 low-risk MDS patients with low platelet levels. Each patient received 750 μg of Nplate either once a week as subcutaneous (under the skin) injection, twice a week as subcutaneous injection, or twice a week as intravenous (into a vein) injection for eight weeks.  Patients could opt to continue the Nplate regimen during a year-long extension phase.

Of the 23 patients who completed the study, 57 percent showed a complete platelet response, and 8 percent had a major platelet response.  Sixty-one percent of patients did not require platelet transfusions during the study.

Researchers found that the weekly subcutaneous dosing resulted in a longer duration of response than biweekly dosing.

Most patients (93 percent) reported side effects, with the most common being headache (18 percent) and fatigue (18 percent).

The only instance of a severe treatment-related side effect was a serious allergic reaction in one patient who received the intravenous injection. After switching from intravenous to subcutaneous administration, the patient experienced no further allergic reaction.

Discontinuation of treatment was often due to side effects, but some cases were the result of disease progression.

“The most important advance that can come with romiplostim [Nplate], from the perspective of an MDS patient, is for the drug to get approved by the FDA for the treatment of MDS,” said Dr. Sekeres.

For more information, please refer to the study in Cancer (abstract).

via mdsbeacon.com