PMID- 37213300
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230523
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - Novel infusion strategy reduces severe adverse events caused by the anti-GD2 
      monoclonal antibody naxitamab.
PG  - 1164949
LID - 10.3389/fonc.2023.1164949 [doi]
LID - 1164949
AB  - INTRODUCTION: Anti-disialoganglioside 2 (anti-GD2) monoclonal antibodies (mAbs) 
      are associated with Grade >/=3 (>/=G3) adverse events (AEs) such as severe pain, 
      hypotension, and bronchospasm. We developed a novel method of administering the 
      GD2-binding mAb naxitamab, termed "Step-Up" infusion (STU), to reduce the risk of 
      AEs of severe pain, hypotension, and bronchospasm. METHODS: Forty-two patients 
      with GD2-positive tumors received naxitamab under "compassionate use" protocols 
      and administered via either the standard infusion regimen (SIR) or the STU 
      regimen. The SIR comprises a 60-min infusion of 3 mg/kg/day on Day 1 of cycle 1 
      and a 30- to 60-min infusion on Day 3 and Day 5, as tolerated. The STU regimen 
      uses a 2-h infusion on Day 1, initiated at a rate of 0.06 mg/kg/h during 15 min 
      (0.015 mg/kg) and which increases gradually to a cumulative dose of 3 mg/kg; on 
      Days 3 and 5, the 3-mg/kg dose is initiated at 0.24 mg/kg/h (0.06 mg/kg) and 
      delivered in 90 min according to the same gradual-increase strategy. AEs were 
      graded according to Common Terminology Criteria for Adverse Events version 4.0. 
      RESULTS: The frequency of infusions with an associated G3 AE was reduced from 
      8.1% (23/284 infusions) with SIR to 2.5% (5/202 infusions) with STU. The odds of 
      an infusion being associated with a G3 AE reduced by 70.3% with STU vs. SIR (odds 
      ratio: 0.297; p = 0.037). Mean serum naxitamab levels pre- and post-STU (11.46 
      microg/ml pre-infusion; 100.95 microg/ml post-infusion) were within the range reported 
      for SIR. DISCUSSION: The comparable pharmacokinetics of naxitamab during SIR and 
      STU may indicate that switching to STU reduces G3 AEs without impact on efficacy.
CI  - Copyright (c) 2023 Varo, Castaneda, Chamorro, Munoz, Gorostegui, Celma, Lopez, 
      Simao, Perez-Jaume and Mora.
FAU - Varo, Amalia
AU  - Varo A
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
FAU - Castaneda, Alicia
AU  - Castaneda A
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
FAU - Chamorro, Saray
AU  - Chamorro S
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
FAU - Munoz, Juan Pablo
AU  - Munoz JP
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
FAU - Gorostegui, Maite
AU  - Gorostegui M
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
FAU - Celma, Monica S
AU  - Celma MS
AD  - Department of Pharmacy, Pediatric Cancer Center Barcelona (PCCB), Hospital Sant 
      Joan de Deu, Barcelona, Spain.
FAU - Lopez, Sandra
AU  - Lopez S
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
FAU - Simao, Margarida
AU  - Simao M
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
FAU - Perez-Jaume, Sara
AU  - Perez-Jaume S
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
FAU - Mora, Jaume
AU  - Mora J
AD  - Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Deu, Barcelona, 
      Spain.
LA  - eng
PT  - Journal Article
DEP - 20230505
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10196122
OTO - NOTNLM
OT  - GD2 monoclonal antibody
OT  - adverse events
OT  - immunotherapy
OT  - naxitamab
OT  - neuroblastoma
OT  - pharmacodynamics
OT  - pharmacokinetics
COIS- The authors declare that this study received funding from Ymabs therapeutics. The 
      funder had the following involvement in the study: editorial and writing.
EDAT- 2023/05/22 13:04
MHDA- 2023/05/22 13:05
PMCR- 2023/01/01
CRDT- 2023/05/22 11:57
PHST- 2023/02/13 00:00 [received]
PHST- 2023/04/12 00:00 [accepted]
PHST- 2023/05/22 13:05 [medline]
PHST- 2023/05/22 13:04 [pubmed]
PHST- 2023/05/22 11:57 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1164949 [doi]
PST - epublish
SO  - Front Oncol. 2023 May 5;13:1164949. doi: 10.3389/fonc.2023.1164949. eCollection 
      2023.