Immunotherapy with anti‐G_D2 monoclonal antibody in infants with high‐risk neuroblastoma

Abstract

Anti‐GD2 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‐GD2 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‐GD2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m2/cycle) than 3F8, dinutuximab, and dinutuximab beta (70‐100 mg/m2/cycle). HR‐NB in infants proved to be highly curable.

Revolutionizing pediatric neuroblastoma treatment: unraveling new molecular targets for precision interventions

“…Toxicity in infants receiving naxitamab at a higher dosage was comparable to older patients. This is reassuring, as the infant HRNB patients had a high potential for cure ( Kushner et al, 2023 ).…”

From mechanism to therapy: the journey of CD24 in cancer

“…This targeted approach aims to minimize damage to normal tissues, given the restricted expression of GD2 in the body. The clinical application of anti-GD2 antibodies represents a significant advancement in the treatment of certain types of cancer, particularly neuroblastoma (105). Clinical trials have demonstrated that anti-GD2 therapy can significantly prolong the survival of patients with high-risk neuroblastoma (105).…”

“…The clinical application of anti-GD2 antibodies represents a significant advancement in the treatment of certain types of cancer, particularly neuroblastoma (105). Clinical trials have demonstrated that anti-GD2 therapy can significantly prolong the survival of patients with high-risk neuroblastoma (105). The mechanism of action involves antibody-dependent cellular cytotoxicity (ADCC), where the binding of anti-GD2 antibodies to GD2-expressing tumor cells triggers their elimination by natural killer (NK) cells, macrophages, and other immune effector cells (106).…”

Experiences of parents of children receiving immunotherapy for neuroblastoma in China: a qualitative study

“…hypotension [20] and some serious adverse effects,like posterior reversible encephalopathy syndrome [21] ,…”