Dinutuximab Beta Anaphylaxis: Successful Desensitization Using a One‐Bag Protocol in a Pediatric Case

To the Editor: Dinutuximab beta (Qarziba), a monoclonal antibody targeting disialoganglioside (GD2), is a key component of immunotherapy for children with high-risk neuroblastoma and has been shown to significantly improve survival outcomes [1-3]. Despite its clinical benefit, dinutuximab beta is associated with a range of adverse drug reactions, including pain, fever, capillary leak syndrome, and hypersensitivity reactions (HSRs) [3-5]. Although most HSRs are mild to moderate, severe reactions such as anaphylaxis may occur and can lead to treatment discontinuation, particularly in the absence of standardized management strategies [4, 5]. Hypersensitivity reactions to dinutuximab beta are classified as mild, moderate, or severe, with anaphylaxis typically presenting with bronchospasm, urticaria, angioedema, and hypotension [4-6]. Current recommendations advise interruption or permanent discontinuation of therapy in cases of life-threatening reactions [4]. However, given the substantial survival benefit conferred by dinutuximab beta, alternative strategies that allow safe continuation of treatment are clinically important. Here, we report a pediatric case of dinutuximab beta-induced anaphylaxis managed with a modified one-bag desensitization protocol, enabling completion of therapy without further HSRs. A 6-year-old female with high-risk neuroblastoma was scheduled to receive five 35-day cycles of dinutuximab beta. Each cycle consisted of continuous infusion over 10 days, prepared by diluting the drug with 20% albumin and normal saline to a total volume of 144 mL. During the first two cycles, the patient experienced mild pain, urticaria, and angioedema, which were controlled with standard premedication (1 mg/kg, paracetamol at 10 mg/kg, gabapentin 10 mg/kg, and morphine at 0.1 mg/kg every 6 h), allowing treatment completion. On the ninth day of the third cycle, the patient developed acute vomiting, hypotension (80/50 mmHg), generalized urticaria, and facial angioedema during infusion. The clinical presentation was consistent with severe anaphylaxis according to the Brown classification [6]. Intramuscular adrenaline (0.01 mg/kg) was administered promptly, leading to rapid clinical improvement. Serum tryptase levels measured at 1 and 48 h after the reaction were 11.4 and 6.73 µg/L, respectively, fulfilling the consensus diagnostic criteria for anaphylaxis (baseline × 1.2 + 2 ng/mL) [7, 8]. No other medications or foods had been administered in the preceding 4 hours. The case was evaluated by a multidisciplinary Pediatric Oncology and Allergy Council, and dinutuximab beta-induced anaphylaxis was confirmed. Skin prick or intradermal testing was not performed because standardized testing concentrations for dinutuximab beta are not available, and the patient had recently experienced a severe reaction. Although discontinuation of therapy was initially considered, no effective alternative treatment options were available, and the potential negative impact on prognosis was substantial. After detailed counseling and written informed consent from the family, continuation of therapy using a modified desensitization approach was planned. A non-reparable one-bag desensitization protocol was implemented. In this protocol, the infusion was initiated at 0.1 mL/h and gradually increased to 2 mL/h over seven stepwise increments. Using this approach, the patient successfully completed the fourth and fifth cycles of dinutuximab beta without any hypersensitivity reactions, including urticaria or angioedema (Table 1). The fourth cycle was completed over 10 days, 3 h, and 30 min. Thirty-five days later, the final cycle was administered using the same protocol and was likewise completed without any adverse reactions. Notably, none of the hypersensitivity manifestations observed during the initial cycles recurred after implementation of the desensitization protocol. Dinutuximab beta-associated adverse reactions are common due to the immunotoxic nature of anti-GD2 therapy [3-5]. Although most reactions occur early during infusion, the risk persists throughout treatment, as demonstrated in our patient, who developed anaphylaxis late in the third cycle. While current recommendations generally advise discontinuation in cases of severe anaphylaxis, this approach may not always be optimal given the drug's proven survival benefit [3, 4]. In such circumstances, carefully designed desensitization protocols may offer a practical approach to enable treatment continuation. In this case, a stepwise one-bag desensitization protocol allowed completion of subsequent dinutuximab beta cycles without hypersensitivity reactions, including urticaria or angioedema, and without a marked prolongation of the planned infusion duration. To our knowledge, desensitization protocols have been reported for other monoclonal antibodies; however, data specifically addressing dinutuximab beta remain limited [9]. The main limitation of this report is the inability to perform standardized allergy testing for dinutuximab beta hypersensitivity due to the lack of validated concentrations and the proximity of the anaphylactic event. Nevertheless, this case provides important clinical insight into a feasible strategy for managing severe HSRs to dinutuximab beta. If confirmed in larger cohorts, this approach may contribute to the development of standardized protocols enabling the safe continuation of life-saving immunotherapy in children with high-risk neuroblastoma. We would like to thank the patient and her family for giving their consent to use their data. The authors declare no conflicts of interest.