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Eltrombopag
Eltrombopag can provide long-term disease control for chronic/persistent immune thrombocytopenia (ITP), according to research published in Blood.
In the EXTEND study, investigators evaluated patients exposed to eltrombopag for a median of 2.4 years.
Most patients achieved a response to the drug, and more than half of them maintained that response for at least 25 weeks.
More than a third of patients were able to discontinue at least 1 concomitant ITP medication.
Most adverse events (AEs) were grade 1 or 2. However, 32% of patients had serious AEs, and 14% of patients withdrew from the study due to AEs.
This research was sponsored by GlaxoSmithKline, the company that previously owned eltrombopag. Now, the drug is a product of Novartis.
Patients
EXTEND is an open-label extension study of 4 trials (TRA100773A, TRA100773B, TRA102537/RAISE, and TRA108057/REPEAT), which enrolled 302 adults with chronic/persistent ITP.
Patients had completed the treatment and follow-up periods as defined in their previous study protocol and did not experience eltrombopag-related toxicity or other drug intolerance on a prior eltrombopag study. Patients who discontinued a previous study due to toxicity were only eligible if they had received a placebo.
The patients’ median time from diagnosis to enrollment in EXTEND was 58.8 months (range, 9-552). Their median age was 50 (range, 18-86), and 67% were female.
Most patients (70%) had a baseline platelet count below 30×109/L. Thirty-three percent of patients were using concomitant ITP medications, 53% had received at least 3 prior ITP treatments, and 38% had undergone splenectomy.
Treatment
Eltrombopag was started at a dose of 50 mg/day and titrated to 25-75 mg/day or less often based on platelet counts. Maintenance dosing continued after minimization of concomitant ITP medication and optimization of eltrombopag dosing.
The overall median duration of eltrombopag exposure was 2.37 years (range, 2 days to 8.76 years), and the mean average daily dose was 50.2 mg/day (range, 1-75).
One hundred and thirty-five patients (45%) completed the study, and 75 patients (25%) were treated for 4 or more years. The most common reasons for study withdrawal included AEs (n=41), patient decision (n=39), lack of efficacy (n=32), and “other” reasons (n=39).
Safety
AEs leading to study withdrawal (occurring at least twice) included hepatobiliary AEs (n=7), cataracts (n=4), deep vein thrombosis (n=3), cerebral infarction (n=2), headache (n=2), and myelofibrosis (n=2).
The overall incidence of AEs was 92%. The most frequent AEs were headache (28%), nasopharyngitis (25%), and upper respiratory tract infection (23%).
Twenty-six percent of patients had grade 3 AEs, 6% had grade 4 AEs, and 32% had serious AEs. Serious AEs included cataracts (5%), pneumonia (3%), anemia (2%), ALT increase (2%), epistaxis (1%), AST increase, (1%), bilirubin increase (1%), and deep vein thrombosis (1%).
Three percent of patients reported a malignancy while on study, including basal cell carcinoma, intramucosal adenocarcinoma, breast cancer, metastases to the lung, ovarian cancer, squamous cell carcinoma, transitional cell carcinoma, lymphoma, unclassifiable B-cell lymphoma (low grade), and Hodgkin lymphoma.
Efficacy
In all, 85.8% (259/302) of patients had a response to eltrombopag, which was defined as achieving a platelet count of at least 50×109/L at least once without rescue therapy.
Fifty-two percent (133/257) of patients achieved a continuous response lasting at least 25 weeks.
Thirty-four percent (34/101) of patients who were on concomitant ITP medication discontinued at least 1 medication. Thirty-nine percent (39/101) reduced or permanently stopped at least 1 ITP medication without receiving rescue therapy.
Fifty-seven percent of patients (171/302) had bleeding symptoms at baseline. This decreased to 16% (13/80) at 1 year.
“The EXTEND data published in Blood validate [eltrombopag] as an important oral treatment option that, by often increasing platelet counts, significantly decreased bleeding rates and reduced the need for concurrent therapies in certain patients with chronic/persistent immune thrombocytopenia,” said study author James Bussel, MD, of Weill Cornell Medicine in New York, New York.
“With this information, physicians can better optimize long-term disease management for appropriate patients living with this chronic disease.”
