Outpatient administration of naxitamab in combination with granulocyte‐macrophage colony‐stimulating factor in patients with refractory and/or relapsed high‐risk neuroblastoma: Management of adverse events

Abstract

Background Naxitamab is a humanized GD2‐binding monoclonal antibody that received accelerated approval from the U.S. Food and Drug Administration for refractory or relapsed high‐risk neuroblastoma limited to bone or bone marrow. Trial 201 (NCT03363373) is an ongoing global clinical trial to evaluate the efficacy and safety of naxitamab in combination with granulocyte‐macrophage colony‐stimulating factor in this population. Aims Here, we review the safety profile and adverse event (AE) management associated with naxitamab administration in a pediatric population, based on Trial 201 protocol guidelines and clinical trial experience. Methods and Results At least 50% of patients experienced pain, hypotension, bronchospasm, cough, vomiting, diarrhea, nausea, and tachycardia, with the following reported at grade ≥3 AEs for at least 10% of patients: pain, hypotension, urticaria, and bronchospasm. These AEs were generally manageable in the outpatient setting using premedications, supportive therapies, and appropriate monitoring post‐infusion. Algorithms were established for infusion‐related AEs, including hypotension and bronchospasm, to provide guidance to investigators for early recognition and timely intervention, including medication and infusion rate modification or interruption, or treatment discontinuation, based on AE severity. Educating patients and caregivers on what to expect regarding premedication at home, experience during the infusion cycle, and post‐infusion monitoring helps optimize naxitamab treatment and supportive therapies and may reduce treatment burden. Conclusion This article highlights the protocol‐based recommendations for the management of acute AEs associated with outpatient naxitamab treatment in Trial 201. The authors recommend close monitoring and timely implementation of measures to ensure that patients can remain on treatment and obtain maximum clinical benefit from naxitamab therapy.

GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma

“…Ongoing research is further evaluating using anti‐GD2 mAbs plus GM‐CSF as part of HR‐NB induction regimens 87,122 . Efforts are also underway to improve management of anti‐GD2‐based immunotherapy‐related toxicities, 123–125 and newer anti‐GD2 mAb generations are being designed to improve upon toxicity profiles of their predecessors 126,127 . Other data have shown similar survival rates for patients receiving post‐induction immunotherapy with anti‐GD2 mAbs and GM‐CSF regardless of whether the patients underwent autologous HCT or not 128–131 .…”

Acute myocarditis with transient myocardial thickening in two oncologic patients treated with anti‐GD2 immunotherapy

“…It is not usual to find adverse effects of autoimmune reactions as in classic ICIs. 8 The peculiarity of case 1 lies in the pre-existing HCM condition, which generated diagnostic controversy as to whether there was a progression of the HCM or a myocarditis induced by immunotherapy. Cardiac MRI, response to treatment, and evolution confirmed the diagnosis of myocarditis induced by anti-GD2 immunotherapy.…”

Pain mitigation and management strategies for anti‐GD2 infusions: An expert consensus

“…However, the 15 mg/kg dose used may also contribute to pain relief during and after anti‐GD2 infusion and may help reduce the total opiate dose required 27 . Nonsteroidal anti‐inflammatory drugs (NSAIDs) can be given for additional pain relief 31,32 . However, NSAIDs should be administered with caution in patients with renal impairment and should be avoided in patients with a low platelet count.…”

“…27 Nonsteroidal anti-inflammatory drugs (NSAIDs) can be given for additional pain relief. 31,32 However, NSAIDs should be administered with caution in patients with renal impairment and should be avoided in patients with a low platelet count.…”