Danyelza

Neuroblastoma is the most common extracranial solid tumor in childhood with 90% of cases diagnosed at younger than 5 years of age. The yearly incidence is approximately 10.54 cases per 1 million in children younger than 15 years and prevalence about 1 case per 7,000 live births. The neuroblastoma originates in the adrenal medulla or the paraspinal sites where sympathetic nervous system tissue resides. Patients commonly present with an abdominal mass and up to 70% have metastatic disease at diagnosis. Prognosis depends on patient age, site of the primary tumor, tumor histology, regional lymph node involvement, stage of disease, response to treatment, and biological features. Naxitamab-gqgk (Danyelza) is FDA-approved in combination with granulocyte-macrophage colonystimulating factor (GMCSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. The FDA-indication is contingent upon clinical benefit in confirmatory trials. Naxitamab-gqgk is a recombinant humanized monoclonal antibody that binds to the glycolipid disialoganglioside (GD2). This glycolipid is overexpressed on neuroblastoma cells and on normal cells of neuroectodermal origin, including the central nervous system and peripheral nerves. GD2 binding induces cell lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The efficacy of naxitamab-gqgk was evaluated in patients with relapsed or refractory neuroblastoma in the bone or bone marrow in two single-arm, open-label trials (study 1 and study 2). Patients with progressive disease following their most recent therapy were excluded. All patients had received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to trial enrollment. Patients were permitted to receive pre-planned radiation to the primary disease site in study 1 and radiation therapy to non-target bony lesions or soft tissue disease in study 2. Among 22 patients in study 1, there were 64% with refractory disease, 36% with relapsed disease and the median age was 5 years (range 3 to 10 years). In study 2, there were 38 patients of which 55% had relapsed neuroblastoma, 45% with refractory disease, and the median age was 5 years (range 2 to 23 years). Both trials included patients with prior treatments such as surgery, chemotherapy, radiation, autologous stem cell transplant, or prior anti-GD2 antibody treatment. The main efficacy outcome measures were confirmed overall response rate (ORR) per the revised International Neuroblastoma Response Criteria (INRC) and duration of response (DOR). In study 1, the ORR was 45% (95% CI: 24%, 68%) and 30% of responders had a DOR greater or equal to 6 months. In study 2, the ORR was 34% (95% CI: 20%, 51%) with 23% of patients having a DOR greater or equal to 6 months. For both trials, responses were observed in either the bone, bone marrow or both. Serious adverse reactions occurred in both studies and the most frequently occurring in study 1 included anaphylactic reaction (12%) and pain (8%) and in study 2 were hypertension (14%), hypotension (11%), and pyrexia (8%) Naxitamab-gqgk contains a black box warning for serious infusion-related reactions including cardiac arrest, anaphylaxis, hypotension, bronchospasm and stridor. It also contains a black box warning for severe neurotoxicity, transverse myelitis and reversible leukoencephalopathy syndrome (RPLS). Premedications are required to prevent infusion reactions, neuropathic pain, and nausea/vomiting.