Immunotherapy with anti‐G D2 monoclonal antibody in infants with high‐risk neuroblastoma

Abstract Anti‐G D2 monoclonal antibodies (mAb) improve the prognosis of high‐risk neuroblastoma (HR‐NB). Worldwide experience almost exclusively involves toddlers and older patients treated after multimodality or second‐line therapies, that is, many months postdiagnosis. In contrast, at our center, infants received anti‐G D2 mAbs because this immunotherapy started during or immediately after induction chemotherapy. We now report on the feasibility, safety, and long‐term survival in this vulnerable age group. Thirty‐three HR‐NB patients were <19 months old when started on 3F8 (murine mAb; n = 21) or naxitamab (humanized‐3F8; n = 12), with 30″ to 90″ intravenous infusions. Patients received analgesics and antihistamines. Common toxicities (pain, urticaria, cough) were manageable, allowing outpatient treatment. Capillary leak, posterior reversible encephalopathy syndrome, and mAb‐related long‐term toxicities did not occur. Two 3F8 cycles were aborted due to bradycardia (a preexisting condition) and asthmatic symptoms, respectively. One patient received ½ dose of Day 1 naxitamab because of hypotension; full doses were subsequently administered. Post‐mAb treatments included chemotherapy, radiotherapy, and anti‐NB vaccine. Among 3F8 patients, 17/21 are in complete remission off all treatment at 5.6+ to 24.1+ (median 13.4+) years from diagnosis. Among naxitamab patients, 10/12 remain relapse‐free post‐mAb at 1.7+ to 4.3+ (median 3.1+) years from diagnosis. Toxicity was similar with short outpatient infusions and matched that observed with these and other anti‐G D2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m 2 /cycle) than 3F8, dinutuximab, and dinutuximab beta (70‐100 mg/m 2 /cycle). HR‐NB in infants proved to be highly curable.