(75) Dinutuximab desensitization in patients with Refractory/Relapsed Neuroblastoma

Title: Dinutuximab desensitization in patients with Refractory/Relapsed Neuroblastoma

Abstract : Neuroblastoma is the most common extracranial tumor in children and continues to be responsible for approximately 15% of the pediatric deaths from cancer each year. Approximately 50% of patients diagnosed with high-risk neuroblastoma have disease that evades our most active treatments and recurs/progresses despite antitumor therapy. Dinutuximab, a GD2 directed monoclonal antibody, is integral in the treatment of relapsed/refractory high-risk neuroblastoma. Unfortunately, Dinutuximab therapy is associated with severe allergic symptoms in up to 26% of patients, manifested in bronchospasm, angioedema, and anaphylaxis. Historically, patients who experience severe allergic symptoms often require administration of epinephrine and discontinuation of this treatment. Since it is well known that dinutuximab positively impacts outcomes in patients with high-risk disease, it is paramount to find creative solutions that allow patients with past allergic reactions to the drug to continue receiving this critical immunotherapy.  The Children’s Hospital of Philadelphia is a large urban pediatric medical center that sees over 650 new oncology patients each year and serves a large population of patients with neuroblastoma.  We developed a multidisciplinary team including oncologists, advanced practice nurses, oncology nurses, allergists, and pharmacists to develop a desensitization protocol that would enable patients with previous severe allergic symptoms an opportunity to continue this therapy. We have been utilizing this desensitization protocol since August 2021 and thus far have treated six patients with this therapy ranging from 1 cycle to 14 cycles. Dinutuximab is infused over approximately 19.5 hours utilizing three bags of dinutuximab containing increasing concentrations of drug. Nursing increases the infusion rate at twelve different time points throughout the infusion. Our supportive care is generalized to include antihistamines, an H2 antagonist, antipyretics, intravenous hydration with frequent addition of bronchodilators. All six of our patients were able to continue their dinutuximab therapy without experiencing severe allergic symptoms while utilizing the desensitization protocol.