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Clinical Trial Results Reveal Safety Issues With Nplate In Lower-Risk MDS Patients (ASH 2011)

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Published: Feb 9, 2012 4:38 pm
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].”

For more information, please see abstract 117 at the ASH 2011 meeting website, as well as the official Nplate prescribing information (PDF).

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2 Comments »

  • Jack seltzer said:

    I am a MDS patient diagnosed with secondary MDS (assumed to occur from treatment for multiple myeloma,
    for which I am in complete remission with test results indicating my remission may well be permanent). On your site you state that the use of Nplate for MDS to increase platelets should not be used while on http://www.cancer.com it is
    stated that Nplate has recently been used for patients with success (2012 date). Please explain. I would like to be able to switch from dacogen, which has been very good in platelet increase (temporarily for ~6 months) but the side effect of a steep decline in energy lasting for weeks to a month is tough to deal with.

    Also, I read that there is also a chance of plate causing a problem in the bone marrow (forget the name for it…something
    like clotting?) for which there is no cure, but I also heard that the testing of Nplate on MDS patients was done on patients who were not tested for this marrow clotting problem before the Nplate trial which means that some of, if not all of the patients in the trial may have had the clotting problem (again I don’t remember the coorrect name fit this) prior to going on Nplate. Comment please.

  • Linda Vuong said:

    Dear Jack,

    We are very sorry to hear that you have been diagnosed with secondary MDS.

    Nplate is currently approved by the FDA for the treatment of low platelet levels in patients with chronic immune thrombocytopenia. It is not officially approved for use in MDS patients but it is being investigated in this patient population.

    As indicated in our article, based on recent research in MDS, a safety warning has been added to the Nplate official prescribing information highlighting that Nplate is not approved for use in MDS patients and that its use in patients with MDS may lead to progression to acute myeloid leukemia:

    http://www.nplate.com/patient/how-nplate-may-help/nplate-side-effects.html

    Even though a drug may be effective in treating a condition, it can be associated with significant risks, as seems to be the case with Nplate in MDS.

    As for using Nplate instead of Dacogen, we recommend speaking with your doctor about this because the two drugs work very differently. Dacogen works by removing methyl groups from DNA, leading bone marrow cells to either mature properly or die. Dacogen’s effects are not on platelets alone. Nplate, on the other hand, is a synthetic version of thrombopoietin, a protein that signals the bone marrow to make more platelets.

    Finally, Nplate can put you at higher risk for getting blood clots and can also change your bone marrow to cause myelofibrosis. If Nplate is causing a patient to develop myelofibrosis, this may show up in blood tests. A doctor can decide if any abnormal blood cell counts are being caused by myelofibrosis and if Nplate use should be stopped.

    Please let us know if you have any other questions about Nplate or anything else.