Dosing and monitoring recommendations for luspatercept in TDT
| Item . | Guidance . |
|---|---|
| Dose increase and discontinuation according to treatment response | • Starting dose of 1 mg/kg subcutaneously every 3 weeks. • Dose increase to 1.25 mg/kg if patient has no reductiona in transfusion burden after at least 2 consecutive doses (6 weeks) of 1 mg/kg. • Treatment discontinuation if patient has no reduction in transfusion burden after 3 consecutive doses (9 weeks) of 1.25 mg/kg (minimum overall treatment duration of at least 15 weeks). |
| Dose titration based on predose hemoglobin or rapid hemoglobin increase | • Treatment interruption if predose hemoglobin ≥11.5 g/dL in the absence of transfusions. Treatment can be restarted when hemoglobin ≤11 g/dL. • Dose decrease if increase in hemoglobin >2 g/dL within 3 weeks and in the absence of transfusions (decrease 1.25 mg to 1.0 mg, 1 mg to 0.8 mg, 0.8 mg to 0.6 mg,b interrupt if 0.6 mg). |
| Adverse event management | • Mild adverse events are generally manageable with over-the-counter analgesics/medications. • For patients who experience persistent high-grade adverse events: º Treatment may be interrupted until the adverse event resolves º Dosage may be modified º Treatment may be discontinued º Individual patient assessment and close monitoring are essential • Treatment should be discontinued for grade 3 or 4 hypersensitivity reactions |
| Adverse events of special interest | • Thromboembolic events: considering the higher number of thromboembolic events observed in luspatercept-treated vs placebo patients in the BELIEVE trial, patients should be monitored for signs and symptoms of thromboembolic events and treatment instituted promptly. Thromboembolic risk assessment and prophylaxis in high-risk patients are advised in patients with β-thalassemia (especially splenectomized adults) regardless of luspatercept therapy. • Hypertension: patients treated with luspatercept had an average increase in systolic and diastolic blood pressure of 5 mmHg from baseline: º Treatment must be started only if the blood pressure is adequately controlled º Blood pressure should be monitored before each luspatercept administration º Luspatercept dose may require adjustment or may be delayed, and patients should be treated for hypertension • EMH: cases of EMH were documented during luspatercept therapy across β-thalassemia trials, although these may be attributed to the natural course of the disease. Patients should be monitored at initiation and during treatment with luspatercept for signs and symptoms of EMH masses (paraspinal localization being the most concerning), especially in NTDT or suboptimally treated TDT patients who are naturally at higher risk of EMH. |
| Item . | Guidance . |
|---|---|
| Dose increase and discontinuation according to treatment response | • Starting dose of 1 mg/kg subcutaneously every 3 weeks. • Dose increase to 1.25 mg/kg if patient has no reductiona in transfusion burden after at least 2 consecutive doses (6 weeks) of 1 mg/kg. • Treatment discontinuation if patient has no reduction in transfusion burden after 3 consecutive doses (9 weeks) of 1.25 mg/kg (minimum overall treatment duration of at least 15 weeks). |
| Dose titration based on predose hemoglobin or rapid hemoglobin increase | • Treatment interruption if predose hemoglobin ≥11.5 g/dL in the absence of transfusions. Treatment can be restarted when hemoglobin ≤11 g/dL. • Dose decrease if increase in hemoglobin >2 g/dL within 3 weeks and in the absence of transfusions (decrease 1.25 mg to 1.0 mg, 1 mg to 0.8 mg, 0.8 mg to 0.6 mg,b interrupt if 0.6 mg). |
| Adverse event management | • Mild adverse events are generally manageable with over-the-counter analgesics/medications. • For patients who experience persistent high-grade adverse events: º Treatment may be interrupted until the adverse event resolves º Dosage may be modified º Treatment may be discontinued º Individual patient assessment and close monitoring are essential • Treatment should be discontinued for grade 3 or 4 hypersensitivity reactions |
| Adverse events of special interest | • Thromboembolic events: considering the higher number of thromboembolic events observed in luspatercept-treated vs placebo patients in the BELIEVE trial, patients should be monitored for signs and symptoms of thromboembolic events and treatment instituted promptly. Thromboembolic risk assessment and prophylaxis in high-risk patients are advised in patients with β-thalassemia (especially splenectomized adults) regardless of luspatercept therapy. • Hypertension: patients treated with luspatercept had an average increase in systolic and diastolic blood pressure of 5 mmHg from baseline: º Treatment must be started only if the blood pressure is adequately controlled º Blood pressure should be monitored before each luspatercept administration º Luspatercept dose may require adjustment or may be delayed, and patients should be treated for hypertension • EMH: cases of EMH were documented during luspatercept therapy across β-thalassemia trials, although these may be attributed to the natural course of the disease. Patients should be monitored at initiation and during treatment with luspatercept for signs and symptoms of EMH masses (paraspinal localization being the most concerning), especially in NTDT or suboptimally treated TDT patients who are naturally at higher risk of EMH. |
Per US Food and Drug Administration (FDA) product label. In the European Medicines Agency (EMA) label, a transfusion burden reduction of less than 33% is required.
Luspatercept at a dose of 0.6 mg/kg is approved for TDT patients by the FDA label only; the EMA label states that the lowest dose should be 0.8 mg/kg.
EMH, extramedullary hematopoiesis.
References: Sheth et al43 and Reblozyl packaging information.45,46