Extended Telintra Dosing Improves Blood Cell Counts In Lower-Risk MDS Patients
Published: Oct 3, 2011 10:52 am
Results from a Phase 2 clinical trial indicate that extended dosing of Telintra improves blood cell counts and reduces dependence on red blood cell transfusions in patients with lower-risk myelodysplastic syndromes.
The study’s authors found that a lower dosage given for an additional week during each treatment cycle improved red blood cell counts for a longer time and caused fewer side effects.
“Telintra is the first oral GST P1-inhibitor that has been shown to reduce or eliminate the need for red blood cell transfusions, which potentially would be a significant clinical benefit for myelodysplastic syndromes (MDS) patients,” said the study’s lead author, Dr. Azra Raza of Columbia University.
“Lower-risk MDS patients suffer from the consequences of progressive bone marrow failure, requiring red blood cell transfusion support, and patients may be at risk for infections and bleeding. An oral therapy that can treat the consequences of low blood counts, improve symptoms, and eliminate the need for transfusions will satisfy an unmet medical need and improve the quality of patients’ lives,” Dr. Raza added.
Interim results from this study were presented by Dr. Raza in December at the American Society of Hematology annual meeting (see related Beacon news).
Telintra (ezatiostat hydrochloride) is currently being developed by the California-based biopharmaceutical company Telik as an oral drug for the treatment of MDS. It promotes the growth and maturation of stem cells while also killing off blood cells that do not mature properly (blasts).
In the present study, researchers evaluated two extended dosing schedules of Telintra in 89 lower-risk MDS patients.
The first 14 patients enrolled in the study received 4,500 mg of Telintra daily for either two weeks or three weeks followed by a week off before the start of the next cycle of treatment. To reduce side effects and the number of pills taken each day, all patients enrolled thereafter received lower doses of Telintra. Specifically, half of the patients received 3,000 mg daily for two weeks followed by a week off (dosing schedule 1), and the other half received 2,000 mg daily for three weeks followed by a week off (dosing schedule 2).
The researchers were able to evaluate 30 patients from dosing schedule 1 (3,000 mg for two weeks) for treatment efficacy. They found that 24 percent had improved red blood cell counts, 10 percent had improved white blood cell counts, and 7 percent had improved platelet counts. Seventeen percent experienced improvements in all three counts.
For dosing schedule 2 (2,000 mg for three weeks), the researchers were able to evaluate 31 patients for treatment efficacy. They found that 19 percent had improved red blood cell counts, 27 percent had improved white blood cell counts, and 0 percent had improved platelet counts. No patients had improvements in all three blood cell counts.
“Since MDS patients also may have low white blood cell and platelet levels, Telintra’s ability to improve white blood cell and platelet [counts] could provide a therapeutic advantage over available agents,” said Dr. Raza.
The researchers observed that duration of response for red blood cell counts depended on time of exposure to Telintra. In dosing schedule 1, which had a higher dose but shorter exposure time, the median response duration was 18 weeks. In dosing schedule 2, the exposure time was extended by a week for each treatment cycle, and the median response duration was 46 weeks.
In addition to analyzing the efficacy of the two dosing schedules, the researchers also evaluated patients’ responses based on what therapies they had previously received.
Among patients who had not previously received Revlimid (lenalidomide), Dacogen (decitabine), or Vidaza (azacitidine), 28 percent achieved improved red blood cell counts after Telintra therapy, and 50 percent had reduced needs for transfusions.
In comparison, among patients who were previously treated with Revlimid, 31 percent achieved improved red blood cell counts, 39 percent had reduced needs for transfusions, and 22 percent achieved transfusion independence.
Telintra was not as effective in patients previously treated with Dacogen or Vidaza. Among these patients, 7 percent achieved improved red blood cell counts and 11 percent had reduced needs for transfusions. In addition, previous treatment with Dacogen or Vidaza significantly reduced patients’ duration of response to Telintra (median of 34 weeks versus 46 weeks).
The researchers stated that Telintra was well tolerated with 3 percent of treatment cycles requiring dose reductions, mostly due to nausea, diarrhea, vomiting, and fatigue. In addition, 20 percent of patients experienced abnormal skin odor.
Side effects were more common with higher doses of Telintra. Additionally, prior treatment with Dacogen or Vidaza increased the risk and severity of side effects.
“We believe that dose schedule 2 is the best dose and dose schedule for this investigational drug, and we will be conducting two new studies with dose schedule 2,” concluded Dr. Raza.
The first new study will be for lower-risk MDS patients with the deletion 5q abnormality who have previously failed prior Revlimid therapy. The second new study will be for lower-risk MDS patients without the deletion 5q chromosomal abnormality, for whom Revlimid is not approved.
For more information, please refer to the article in the journal Cancer (abstract).
- Telintra Improves Blood Cell Counts And Is Safe For Lower-Risk MDS Patients (ASH 2010)
- Telintra-Revlimid Combination May Be Effective And Safe In Lower-Risk MDS Patients
- Certain Markers May Predict Telintra Response In Lower-Risk MDS Patients
- ASH 2010 Myelodysplastic Syndromes Update – Day Two
- ASH 2011 Myelodysplastic Syndromes Update – Day 1 & Day 2