In a patient with solid‑tumor chemotherapy‑induced thrombocytopenia persisting ≥4 weeks and platelet count <100 ×10⁹/L, how should romiplostim (Nplate) be initiated, dosed, titrated, and monitored?

Romiplostim for Chemotherapy-Induced Thrombocytopenia

Initiate romiplostim at 1 mcg/kg subcutaneously once weekly in patients with solid tumor chemotherapy-induced thrombocytopenia persisting ≥4 weeks with platelet counts <100 × 10⁹/L, then escalate by 1 mcg/kg weekly increments until platelets reach ≥100 × 10⁹/L, with a maximum dose of 10 mcg/kg per week. 1, 2

Initiation Criteria and Starting Dose

Begin romiplostim when thrombocytopenia has persisted for at least 4 weeks despite chemotherapy delays or dose reductions, and platelet count remains <100 × 10⁹/L. 2 The FDA-approved starting dose is 1 mcg/kg subcutaneously once weekly, calculated using actual body weight at treatment initiation. 1

• However, emerging real-world evidence suggests higher initial doses (2-4 mcg/kg) may be more effective for achieving rapid platelet recovery in CIT, particularly in severe thrombocytopenia. 3
• In the pivotal phase II randomized trial, 93% of romiplostim-treated patients achieved platelet correction within 3 weeks using the 1 mcg/kg starting dose with weekly titration. 2

Dose Titration Protocol

Increase the dose by 1 mcg/kg weekly until platelet count reaches ≥100 × 10⁹/L, which is the target for safe chemotherapy resumption. 1, 2

• The mean effective dose in clinical studies was 2.9 mcg/kg (range 1.0-5.1 mcg/kg) to achieve adequate platelet recovery. 4
• Most patients achieve platelet correction within 2 weeks of initiating romiplostim, with mean platelet counts reaching 141,000/μL by week 2. 2
• Do not exceed a maximum weekly dose of 10 mcg/kg. 1

Specific Dose Adjustments

• If platelet count remains <100 × 10⁹/L: Increase dose by 1 mcg/kg weekly. 1
• If platelet count is >200 × 10⁹/L and ≤400 × 10⁹/L for 2 consecutive weeks: Reduce dose by 1 mcg/kg. 1
• If platelet count exceeds 400 × 10⁹/L: Hold romiplostim and monitor platelet counts weekly; resume at a dose reduced by 1 mcg/kg once platelets fall below 200 × 10⁹/L. 1

Monitoring Requirements

Obtain complete blood counts with platelet counts weekly during the dose adjustment phase until a stable dose is achieved, then reduce monitoring frequency to monthly. 1, 5

• Weekly monitoring is critical during the first 2-4 weeks to guide dose titration and detect early response. 1
• After establishing a stable romiplostim dose that maintains platelets ≥100 × 10⁹/L, transition to monthly CBC monitoring. 5
• Upon discontinuation of romiplostim, obtain weekly CBCs for at least 2 weeks to monitor for rebound thrombocytopenia. 1, 5

Continuation During Chemotherapy

Once platelet counts reach ≥100 × 10⁹/L, resume chemotherapy while continuing weekly romiplostim at the effective dose. 4, 2

• In clinical trials, 70-79% of patients avoided chemotherapy dose reductions or treatment delays when maintained on weekly romiplostim during ongoing chemotherapy. 6, 7
• Only 6.8% of patients experienced recurrent CIT requiring chemotherapy modification when romiplostim was continued weekly during treatment. 2
• Weekly dosing is superior to intermittent or intracycle dosing, with significantly higher response rates and fewer chemotherapy delays (IRR 3.00,95% CI 1.30-6.91). 6

Discontinuation Criteria

Discontinue romiplostim if platelet count does not increase to ≥100 × 10⁹/L after 4 weeks of therapy at the maximum dose of 10 mcg/kg. 1

• Predictors of romiplostim non-response include bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide exposure. 6
• Patients with hematologic malignancies and bone marrow involvement show blunted response (10% response rate) and are poor candidates for romiplostim. 6

Safety Considerations and Pitfalls

Monitor for thrombotic events, though rates appear similar to baseline cancer-associated thrombosis risk (approximately 5-15%). 4, 6

• Three deep vein thromboses occurred in 20 patients in one series, which falls within expected thrombosis rates for patients with active cancer on chemotherapy. 4
• Long-term use (≥1 year) demonstrates sustained efficacy without evidence of resistance or increased thrombotic risk. 7
• Worsening thrombocytopenia may occur upon abrupt discontinuation; gradual tapering is recommended when stopping therapy. 5, 1

Common Adverse Events

• Headache, fatigue, epistaxis, arthralgia, and contusion occur in ≥20% of patients but at similar rates to placebo. 5
• Bone marrow reticulin formation can occur but is typically mild, asymptomatic, and reversible upon treatment interruption. 5

Critical Caveats

Romiplostim is NOT indicated for thrombocytopenia due to myelodysplastic syndrome (MDS), as bone marrow evaluations have revealed transiently increased blast counts raising concerns about progression to acute myeloid leukemia. 1, 5

• The use of very small volumes (e.g., 0.15 mL) requires syringes with 0.01 mL graduations to ensure accurate dosing. 1
• Platelet transfusion thresholds for solid tumor patients remain at 10 × 10⁹/L for prophylaxis, though higher thresholds (20 × 10⁹/L) may be appropriate for patients with necrotic tumors. 8