Romiplostim Research & Studies

Chemotherapy-induced thrombocytopenia (CIT) is a common complication of chemotherapy that is associated with bleeding, reduced relative dose intensity, and potentially worse outcomes. No widely available therapies are approved for CIT.

Thrombocytopenia is a common challenge in the neonatal intensive care unit, traditionally managed with platelet transfusions. However, transfusions are associated with significant risks, including increased mortality and neurodevelopmental impairment. This case series highlights the use of romiplostim, a thrombopoietin receptor agonist, in three neonates with thrombocytopenia. Each case demonstrated notable improvements in platelet counts without adverse events, reducing dependency on transfusions. These findings underscore romiplostim's potential as a safer alternative for managing neonatal thrombocytopenia. This report advocates for further research to explore romiplostim's efficacy and safety in this vulnerable population, emphasizing its promise in improving neonatal outcomes.

Romiplostim has been shown to restore multi-lineage haematopoiesis and is effective in patients with aplastic anaemia (AA) refractory to immunosuppressive therapy (IST). This open-label, phase 2/3 study (NCT04095936) recruited adult AA patients in Japan and Korea who had not received prior IST and evaluated the efficacy and safety of romiplostim plus ciclosporin A (CsA). Romiplostim was initiated at 10 μg/kg once weekly through Week 4 and adjusted between 0 and 20 μg/kg from Week 5 onwards. CsA was administered at 5-6 mg/kg/day in two divided doses through Week 26. A total of 24 patients (median [range] age, 52 [19-80] years) were enrolled, and 22 (91.7%) completed the study. Four patients (16.7%) had very severe AA (VSAA), 13 (54.2%) had severe AA (SAA) and seven (29.2%) had transfusion-dependent non-severe AA (NSAA). A haematological response at Week 27 was observed in 10/24 patients (overall response, 41.7%; 95% confidence interval, 22.1%-63.4%). At Week 27, the subgroup overall response rates were 0.0% in VSAA, 46.2% in SAA and 57.1% in NSAA. Nearly 92% of patients experienced at least one treatment-emergent adverse event (TEAE), but no drug-related Grade ≥3 TEAEs were reported. One patient developed myelodysplastic syndromes. Treatment with romiplostim plus CsA was effective and well tolerated in patients with AA who had not previously received IST.

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Donor-type aplasia (DTA) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by bone marrow hypoplasia despite full chimerism. This report highlights the successful use of romiplostim (ROMI) for treating DTA in three patients with acquired aplastic anemia (AA), including two who were unresponsive to eltrombopag (EPAG). Case 1: A 21-year-old female with non-severe AA, treated with cyclosporine (CsA), rabbit antithymocyte globulin, and EPAG, showed no improvement. After undergoing bone marrow transplantation (BMT) from an HLA-matched sibling, she continued to experience pancytopenia. Switching from EPAG to ROMI 16 months after BMT led to transfusion independence after 7 weeks and normalized blood counts by 17 months. Case 2: A 35-year-old male with moderate AA, initially treated with CsA and ROMI, switched to EPAG before BMT from an HLA-matched sibling. Despite complete donor chimerism, pancytopenia recurred 7 months after BMT. Transitioning from EPAG to ROMI resulted in transfusion independence after 5 months and normalized blood counts after 11 months of ROMI. Case 3: A 25-year-old female with moderate AA, unresponsive to CsA and EPAG, remained transfusion-dependent. Following BMT from an HLA-matched sibling and an initial lack of response to ROMI, restarting ROMI led to transfusion independence after 9 months and normalization of blood counts by day 418 post-BMT. These patients suggest ROMI, particularly at high doses, may be more effective than EPAG for DTA, potentially avoiding the need for a second allo-HSCT. Further studies are required to compare the efficacy of ROMI and EPAG in treating DTA following allo-HSCT.

Romiplostim, a thrombopoietin analog, is commonly used to treat immune-mediated thrombocytopenia (ITP) in humans, but its use in dogs remains limited.

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy delays, dose reductions, and discontinuation. There is no FDA-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at 4 U.S. centers. The primary outcome was achievement of a romiplostim response [median on-romiplostim platelet count (Plt) ≥75x109/L and ≥30x109/L above baseline]. Secondary outcomes included time to Plt≥100x109/L and rates of the following: Plt<100x109/L, Plt<75x109/L, Plt<50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of 4 (range, 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays and 89% avoided platelet transfusions. Median per-patient Plt on romiplostim was significantly higher than baseline (116x109/L vs. 60x109/L, P<0.001). Bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays (IRR 3.00, 95% CI 1.30-6.91, P=0.010) or bleeding (IRR 4.84, 95% CI 1.18-19.89, P=0.029). Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with bone marrow involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.

Thrombocytopenia results from a variety of conditions, including radiation, chemotherapy, autoimmune disease, bone marrow disorders, pathologic conditions associated with surgical procedures, hematopoietic stem cell transplant (HSCT), and hematologic disorders associated with severe aplastic anemia. Immune thrombocytopenia (ITP) is caused by immune reactions that accelerate destruction and reduce production of platelets. Thrombopoietin (TPO) is a critical component of platelet production pathways, and TPO receptor agonists (TPO-RAs) are important for the management of ITP by increasing platelet production and reducing the need for other treatments. Romiplostim is a TPO-RA approved for use in patients with ITP in the United States, European Union, Australia, and several countries in Africa and Asia, as well as for use in patients with refractory aplastic anemia in Japan and Korea. Romiplostim binds to and activates the TPO receptor on megakaryocyte precursors, thus promoting cell proliferation and viability, resulting in increased platelet production. Through this mechanism, romiplostim reduces the need for other treatments and decreases bleeding events in patients with thrombocytopenia. In addition to its efficacy in ITP, studies have shown that romiplostim is effective in improving platelet counts in various settings, thereby highlighting the versatility of romiplostim. The efficacy of romiplostim in such disorders is currently under investigation. Here, we review the structure, mechanism, pharmacokinetics, and pharmacodynamics of romiplostim. We also summarize the clinical evidence supporting its use in ITP and other disorders that involve thrombocytopenia, including chemotherapy-induced thrombocytopenia, aplastic anemia, acute radiation syndrome, perisurgical thrombocytopenia, post-HSCT thrombocytopenia, and liver disease.

Chemotherapy-induced thrombocytopenia (CIT) leads to delay or reduction in cancer treatment. There is no approved treatment.

Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP.