SAN DIEGO—Romiplostim (Nplate), a synthetic protein that binds to and stimulates the thrombopoietin receptor, induced a rapid platelet response in adult patients with primary immune thrombocytopenia (ITP) and maintained a consistent safety profile in an international, phase III, open-label, single-arm, prospective study. The trial involved 407 patients. Findings were reported by Ann Janssens, MD, from the department of hematology, University Hospitals Leuven, Belgium.
Romiplostim stimulates platelet production via the TPO-receptor, and is currently recommended for second- and third-line treatment of chronic ITP in adults. The study enrolled patients with varying degrees of severity of ITP. Dr. Janssen explained that eligibility criteria were broad: patients had to be at least 18 years of age, been given prior ITP therapies, with low platelet counts or experiencing uncontrolled bleeding. The only excluded comorbidities were hematological malignancy, myeloproliferative neoplasms, myelodysplastic syndrome, and bone marrow stem cell disorder.
Romiplostim was initiated at 1 µg/kg/week (final amendment) or 3 µg/kg/week (previous amendments), with dose adjustments allowed to maintain platelet counts ≥ 50 × 109/L. Patients could continue on study until they had access to commercially available romiplostim. Rescue medications were allowed at any time; concurrent ITP therapies could be reduced when platelet counts were > 50 × 109/L.
Primary end point was incidence of adverse events (AEs) and antibody formation. Secondary end point was platelet response, defined as either doubling of baseline count and ≥ 50 × 109/L, or ≥ 20 × 109/L increase from baseline.
Of the 407 patients who received romiplostim, 60% female. Seventy-one percent of patients completed the study. The most common reasons were discontinuation were with requirement for alternative therapy and withdrawn consent (5% each). Duration of treatment ranged from 20 to 201 weeks, with a total of 20,201 subject-weeks on study.
Incidence and type of AEs were consistent with previous studies. The most common side effects included headache, arthralgia, and fatigue. No neutralizing antibodies to romiplostim or TPO were reported.
Eighteen patients died; three of the deaths were considered treatment-related. Approximately 90% of patients achieved each of the platelet response definitions, regardless of splenectomy status. Overall, median time to response was 2 weeks for response definition 1 and 1 week for response definition 2. Median baseline platelet count was. After 1 week of treatment, median platelet count increased from a baseline of 14 × 109/L to 42 × 109/L. From week 8 on (excluding counts within 8 weeks of rescue medication use), median platelet counts were consistently above 100 × 109/L.
“This is the largest prospective study in adult ITP reported to date,” said Dr. Janssens. “Findings confirm those reported for previous studies, with romiplostim able to safely induce a rapid platelet response in adult ITP patients with low platelet counts or bleeding symptoms.
“Romiplostim is an important, well-tolerated, treatment option for adult ITP patients, which significantly increases and maintains platelet counts.”
Updated findings from an open-label extension study evaluating long-term safety and efficacy of romiplostim in 72 thrombocytopenic patients with myelodysplastic syndromes (MDS) were also reported. “Thrombocytopenia, found in 40% to 65% of MDS patients, is an independent risk factor for survival,” explained Pierre Fenaux, MD, PhD, from Hôpital Avicenne, Paris, France.
“In this study of 72 MDS patients, long-term treatment of MDS patients with romiplostim for up to 3.5 years (5 years with prior studies) was well tolerated and resulted in platelet responses in 83% of patients.”