Telintra-Revlimid Combination May Be Effective And Safe In Lower-Risk MDS Patients
Published: May 8, 2012 11:05 am; Updated: May 10, 2012 12:18 pm
Results from a Phase 1 clinical trial suggest that the combination of Telintra and Revlimid may be effective and safe in lower-risk myelodysplastic syndromes patients.
The study investigators found that the combination of Telintra and Revlimid promoted the growth of new blood cells. In addition, several patients who were previously dependent on red blood cell transfusions became transfusion-independent after therapy.
Based on their findings, the investigators conclude that the combination should be further investigated in clinical trials.
“The determination of the optimal doses for the Telintra/Revlimid combination in this Phase 1 study will assist the planning for Phase 2 studies with this combination in MDS and other hematologic malignancies where Revlimid is the standard of care,” said the study’s lead investigator, Dr. Azra Raza of Columbia University.
In myelodysplastic syndromes (MDS), developing blood cells are abnormal and unable to mature into fully functioning blood cells. As a result, many of the symptoms MDS patients experience are due to low blood cell counts.
Telintra (ezatiostat hydrochloride) is currently being developed by the biopharmaceutical company Telik as an oral drug for the treatment of lower-risk MDS. Telintra stimulates the growth and maturation of developing blood cells and kills off cells that are unable to properly mature.
Results of a previous Telintra trial showed a high transfusion independence rate in patients who had previously been treated with Revlimid (lenalidomide) (see related Beacon news), which, according to the study investigators, suggests a potential for the two drugs to be given in combination.
“The unique mechanism of action of Telintra and its generally well tolerated toxicity profile with lack of [decreased blood cell counts] makes it an ideal drug candidate for testing in potential combinations with drugs such as Revlimid,” explained Dr. Raza.
The investigators therefore conducted a Phase 1 study to evaluate the combination of Telintra and Revlimid in lower-risk MDS patients.
The study included 19 patients with a median age of 75 years; 68 percent of the patients were transfusion-dependent at the start of the study.
The patients received either 2,000 mg or 2,500 mg of Telintra daily plus 10 mg of Revlimid on days 1 to 21 of a 28-day treatment cycle.
The investigators found that 25 percent of evaluable patients in the 2,500 mg/10 mg dose group and 40 percent of evaluable patients in the 2,000 mg/10 mg dose group showed improved red blood cell counts. Sixty percent of patients with low platelet counts experienced a platelet response.
Of the patients who were dependent on red blood cell transfusions, 43 percent became transfusion-independent, including one patient who previously underwent ineffective Revlimid single-agent therapy.
According to the investigators, the observed side effects were consistent with those expected for the individual drugs. The most common non-blood-related side effects for the Telintra/Revlimid combination were mild to moderate fatigue, anorexia, nausea, diarrhea, and vomiting. The most common blood-related side effects were low platelet, white blood cell, and red blood cell counts, which are frequently seen with Revlimid therapy.
Due to dose-limiting side effects in several patients, the investigators determined the optimal dosing of Telintra to be 2,000 mg daily in this combination.
For more information, please refer to the study in the Journal of Hematology & Oncology (abstract).
- Telintra Improves Blood Cell Counts And Is Safe For Lower-Risk MDS Patients (ASH 2010)
- Extended Telintra Dosing Improves Blood Cell Counts In Lower-Risk MDS Patients
- Revlimid-Velcade Combination May Be Effective And Safe For MDS (ASCO 2012)
- Vidaza Followed By Revlimid May Be Effective In Certain Higher-Risk MDS Patients
- Certain Markers May Predict Telintra Response In Lower-Risk MDS Patients