Active Ingredient: Dinutuximab
Dinutuximab is indicated for the treatment of high-risk neuroblastoma in patients aged 12 months and above, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with history of relapsed or refractory neuroblastoma, with or without residual disease. Prior to the treatment of relapsed neuroblastoma, any actively progressing disease should be stabilised by other suitable measures.
In patients with a history of relapsed/refractory disease and in patients who have not achieved a complete response after first line therapy, dinutuximab should be combined with interleukin-2 (IL-2).
For this indication, competent medicine agencies globally authorize below treatments:
For:
Regimen A: Intravenous, 10 milligrams dinutuximab per square meter of body surface, once daily, 10 doses in total, over the duration of 35 days. This step is repeated 5 times.
Regimen B: Intravenous, 20 milligrams dinutuximab per square meter of body surface, once daily, 5 doses in total, over the duration of 35 days. This step is repeated 5 times.
Treatment with dinutuximab consists of 5 consecutive courses, each course comprising 35 days. The individual dose is determined based on the body surface area and should be a total of 100 mg/m² per course.
Two modes of administration are possible:
When IL-2 is combined with dinutuximab, it should be administered as subcutaneous injections of 6×106 IU/m²/day, for 2 periods of 5 consecutive days, resulting in an overall dose of 60×106 IU/m² per course. The first 5-day course should start 7 days prior to the first infusion of dinutuximab beta and the second 5-day course should start concurrently with dinutuximab beta infusion (days 1 to 5 of each dinutuximab beta course).
Prior to starting each treatment course, the following clinical parameters should be evaluated and treatment should be delayed until these values are reached:
Based on the physician’s evaluation of the severity of adverse drug reactions to dinutuximab beta, patients may undergo a dose reduction of 50% or a temporary interruption of the infusion. As a consequence, either the infusion period is prolonged or, if tolerated by the patient, the infusion rate may be increased up to 3 mL/h (continuous infusion), in order to administer the total dose.
Recommended dose modifications for dinutuximab beta:
| Adverse reaction | Severity | Treatment modification |
|---|---|---|
| Any | Grade 1-2 | Decrease infusion rate to 50%, After resolution, resume infusion at original rate |
| Hypersensitivity reaction | e.g. hypotension | Interrupt infusion and administer supportive measures, After resolution, resume infusion at original rate |
| Dilated pupils with sluggish light reflex +/- photophobia | Interrupt infusion, After resolution, resume infusion at 50% rate | |
| Any | Grade ≥3 | Interrupt infusion and administer supportive measures, Resume infusion at 50% rate if ADR resolves or improves to Grade 1-2, After resolution, increase to original rate |
| Recurrent | Discontinue infusion, Resume next day if ADR resolves | |
| Hypersensitivity reaction | e.g. bronchospasm, angioedema | Interrupt infusion immediately and treat appropriately, Resume treatment for subsequent courses |
| Capillary leak syndrome | Interrupt infusion and administer supportive measures, Resume at 50% rate if ADR resolves or improves to Grade 1-2 | |
| Central neurotoxicity | Interrupt infusion immediately, rule out other influencing factors and treat appropriately. There is limited data available on resuming treatment and no recommendations can be made | |
Treatment with dinutuximab beta should be permanently discontinued if the following toxicities occur:
Dinutuximab is for intravenous infusion. The solution should be administered via a peripheral or central intravenous line. Other intravenously co-administered agents should be delivered via a separate infusion line.
For continuous infusions, the solution is administered at a rate of 2 mL per hour (48 mL per day) using an infusion pump.
For 8-hour daily infusions, the solution is administered at a rate of approximately 13 mL per hour.
Pre-medication should always be considered before starting each infusion.
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