Exploring a New Indication for Romiplostim: Correcting and Preventing Chemotherapy-Induced Thrombocytopenia

Many patients with cancer receiving chemotherapy will experience chemotherapy-induced thrombocytopenia (CIT), which can lead to dose delays or reductions. In an open-label, phase II study presented at the 2017 ASH Annual Meeting, researchers reported that the thrombopoietin receptor agonist romiplostim could correct and prevent recurrence of CIT, compared with observation only.

Romiplostim is U.S. Food and Drug Administration–approved to treat immune thrombocytopenia. The results from this study explored a new indication for romiplostim, lead author Gerald A. Soff, MD, of the Department of Medicine, Hematology Service at Memorial Sloan Kettering Cancer Center in New York, noted during his presentation.

“We’re addressing what I think of as ‘the holy grail’ in supportive care,” he told ASH Clinical News. “We can fix neutropenia with granulocyte colony stimulating factor, we can fix anemia with transfusions, but we have no good options for thrombocytopenia. [With these data], we have a very clear signal that we’re on the right path.”

The study included 40 patients (mean age = 58 years; range = 28-77 years) with solid-tumor cancers, most of whom had gastrointestinal (GI) cancer (n=22). Most people had metastatic disease (n=35); the remaining patients had locally advanced disease (n=5).

Only patients who had previously experienced at least four weeks of CIT (defined as a platelet count <100,000/mcL), despite reductions or delays in chemotherapy, were included in the trial. They were then randomized 2:1 to receive weekly romiplostim or observation only. Patients in the observation cohort whose platelet counts failed to correct to >100,000/mcL within three weeks (primary endpoint) were permitted to crossover to the romiplostim cohort.

By the time eight patients were enrolled in the observation cohort, an unplanned interim analysis revealed “a notable difference in platelet transfusion requirements during that three-week period,” Dr. Soff said. “At that point, we dropped the observation arm with approval of the institutional review board and the rest of the patients received romiplostim upfront.”

Of the 32 patients who received upfront romiplostim, the platelet counts of 27 (84%) corrected to >100,000/mcL within three weeks (see TABLE). Among the five people whose platelet counts failed to return to >100,000/mcL, two had protocol violations because chemotherapy was prematurely resumed prior to platelet correction.

Twenty-five patients resumed chemotherapy after CIT correction, and weekly romiplostim was titrated to a target platelet count of 150,000/mcL. The mean effective romiplostim dose for platelet count correction was 2.5 mcg/kg (range = 1.8-4.1 mcg/kg). Only one patient had CIT recurrence after resuming chemotherapy.

Romiplostim was well tolerated, Dr. Soff said, with no evidence of bone marrow–related adverse events (AEs). Patients receiving romiplostim reported the following AEs: thrombosis (n=4; 12.5%), including one symptomatic pulmonary embolism (PE), one incidentally identified PE, and two deep vein thromboses. The thrombosis rate was “well within the expected range for patients with metastatic cancers,” he added.

Three patients in the romiplostim cohort required platelet transfusions: One patient had an upper GI bleed from a gastric tear, and two received platelet transfusion during terminal hospitalizations for progression of disease.

“Several patients have been treated for well over a year,” Dr. Soff noted, and one patient remained on romiplostim for more than three years. The tolerability suggests “a durable benefit to the patients,” he added.

The study is limited by its single-center design and the small patient population, Dr. Soff noted, and the results are not generalizable to patients with hematologic malignancies. “We are planning a randomized, placebo-controlled, phase III study with the primary goal of correcting and maintaining platelet counts with resumption of chemotherapy,” he said. “We’re also hoping to demonstrate the value of maintaining full-dose chemotherapy on schedule. One would assume there is, but we have to clearly and prospectively demonstrate [this benefit].”

Dr. Soff reports receiving financial support from Janssen and Amgen.


Soff GA, Miao Y, Devlin SM, et al. Romiplostim for chemotherapy-induced thrombocytopenia (CIT).  Results of a phase 2 trial. Abstract #289. Presented at the 2017 American Society of Hematology Annual Meeting, December 10, 2017; Atlanta, GA.