#2668 New treatments, new challenges: nephrotoxicity associated to naxitamab in patients with high-risk neuroblastoma

Abstract

Abstract Background and Aims Neuroblastoma is the most common extracranial solid tumor in children, harboring a poor survival for those with high-risk (HR) tumors. Naxitamab (hu3F8) is a humanized monoclonal anti-disialoganglioside (GD2) antibody approved for the treatment of patients older than 1-year with refractory/relapsed HR-neuroblastoma limited to bone and/or bone marrow. First naxitamab (DanyelzaR) infusion was in 2017 in our institution and since then a large experience has been acquired with its use through several clinical trials as well as an expanded named patient access program. The objective is to describe the renal toxicity profile associated to naxitamab in patients with HR-neuroblastoma. Method Retrospective descriptive study including 244 patients treated with naxitamab (either on monotherapy or associated to chemotherapy) from June 2017 to December 2022 in whom renal involvement and/or hypertension (HT) was evaluated. Results Mean age of the cohort was 8 years (41% female -101- and 59% male -143-), presenting nephrotoxicity of some type up to 26.6% (n = 65): AHT (11.9%), acute renal damage (ARD 10.2%) and proteinuria (5.3%), developing all during the first 3 cycles. All of them were classified as mild adverse events (1-2) according to the Common Terminology Criteria for Adverse Events (CTCAE) scale, except for one patient with ARD grade 3 and two patients with HT grade 3. In the case of HT only in 6 patients an Ambulatory Blood Pressure Monitoring (ABPM) was performed, observing: 2 nocturnal-HT, 2 diurnal-HT without specific-pattern and 2 disautonomic-patterns. Among the ARD, all cases were tubular except for two patients who presented acute tubule-interstitial nephritis (AIN) (one with clinical-analytical pattern and another confirmed by biopsy). Eight of them (32%) had potential confounding factors (previous chemotherapy, ibuprofen or radiotherapy). Among patients with proteinuria (none in the nephrotic range): 38% tubular, 38% glomerular and 23% mixed. Two patients presented ARD + HT and 3 a combination of HT + ARD + proteinuria. All patients received prior chemotherapy and 2 developing chronic renal damage (CKD stage 2 and 3). Conclusion Short-and long-term follow-up, the systematic performance of ABPM, and the use of early markers of renal damage, could lead to a more efficient management of complications derived from this new treatment.