A Single Institutional Experience Using Romiplostim to Manage Treatment Related Thrombocytopenia in Pediatric Solid Tumor Patients

Background: Therapy related thrombocytopenia (TRT), particularly chemotherapy induced thrombocytopenia (CIT), is a common toxicity encountered by pediatric solid tumor patients. It is associated with both reduced relative dose intensity of chemotherapy treatment as well as increased platelet transfusion requirements. Given the utility of thrombopoietin receptor (TPO-R) agonists in adult CIT and the reassuring safety profile in pediatric immune thrombocytopenia (ITP), romiplostim has been widely used in our department for management of TRT. This study describes our single institution experience of the off-label use of romiplostim for TRT in pediatric solid tumor patients.

Methods: This study retrospectively evaluated solid tumor patients (sarcomas, high-risk neuroblastoma, and CNS tumors) treated at Memorial Sloan Kettering Cancer Center between 2010-2022 who received romiplostim during their cancer therapy for TRT. TRT was defined as thrombocytopenia attributed to cancer-directed therapy that persisted despite adequate recovery time and/or resulted in treatment modifications. Baseline data (Table 1) was collected on patient demographics, tumor types, cancer therapy, and dosing and duration of romiplostim administration. The primary endpoint was impact of romiplostim on TRT measured through (1) the median platelet count throughout romiplostim treatment, (2) the time-to-platelet count recovery after initiation of romiplostim (defined by platelet count of ≥75 µ/L), (3) the median number of platelet transfusions while on romiplostim. Safety data was also collected on incidence of venous thromboembolism (VTE) development during romiplostim treatment.

Results: A total of 62 patients were included with mean age 8.5 years (range: 1.0 to 30.0 years). The overall median time on romiplostim was 17 weeks (range 1-95). The median starting dose ranged from 1-5 mcg/kg, with the majority (81%) starting at 3 mcg/kg and a median maximum dose of 8mcg/kg. There was an upward trend of platelet counts over time with a sustained response measured 30 days post-romiplostim discontinuation (Figure 1). Disease subgroup was a predictor of platelet counts while on romiplostim as the patients with sarcomas had higher counts compared to the other histologic subgroups (p < 0.001). Within the neuroblastoma cohort, there appears to be a difference in platelet response depending on type of cancer-directed therapy, with chemo and immunotherapy groups exhibiting a higher response than the radionuclide group. Of the total 62 patients, 48 (77%) experienced a platelet recovery and the median measured time-to-recovery was 45 days; with the sarcoma patients experiencing the earliest time-to-recovery with a median time of 8 days (p < 0.001). In assessing incidence of adverse events, of the 62 studied patients, 2 (3%) were noted to be on anticoagulation for a documented VTE while on romiplostim.

Conclusions: Given such paucity of available data in pediatrics, the purpose of this retrospective study was to provide insight into the off-label use of romiplostim in pediatric oncology patients. From the analysis of the 62 patients treated with romiplostim during their cancer treatment course, it appears that romiplostim was well tolerated and exhibited potential in providing clinical benefit. While the length of romiplostim treatment varied depending on the specifics of a patient's cancer-directed therapy, overall, the median time on romiplostim was approximately 4 to 5 months with some patients being notably treated for > 1 year. Future, prospective studies are warranted to study the efficacy of using TPO-R agonists in pediatric oncology patients for the indication of TRT.

Modak:YMAbs Therapeutics: Consultancy; US WorldMeds: Consultancy; Inervate Radiopharma: Consultancy. Dunkel:Bristol Myers Squibb, Astra Zeneca, Day One, QED: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mones:Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees. Ortiz:Amgen: Research Funding.

Romiplostim for pediatric chemotherapy induced thrombocytopenia