Immunotherapy with anti-G(D2) monoclonal antibody in infants with high-risk neuroblastoma Journal Article
| Authors: | Kushner, B. H.; Modak, S.; Kramer, K.; Basu, E. M.; Iglesias-Cardenas, F.; Roberts, S. S.; Cheung, N. K. V. |
| Article Title: | 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 1⁄2 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. © 2022 UICC. |
| Keywords: | aged; antineoplastic agents; antineoplastic agent; mouse; animal; animals; mice; neoplasm recurrence, local; monoclonal antibody; antibodies, monoclonal; immunotherapy; infant; neuroblastoma; tumor recurrence; immunologic factors; immunologic factor; 3f8; posterior reversible encephalopathy syndrome; posterior leukoencephalopathy syndrome; infants; humans; human; naxitamab |
| Journal Title: | International Journal of Cancer |
| Volume: | 152 |
| Issue: | 2 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2023-01-15 |
| Start Page: | 259 |
| End Page: | 266 |
| Language: | English |
| DOI: | 10.1002/ijc.34233 |
| PUBMED: | 35913764 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and in the PDF -- Corresponding author is MSK author Brian H. Kushner -- Export Date: 1 December 2022 -- Source: Scopus |
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