PMID- 37561984
OWN - NLM
STAT- MEDLINE
DCOM- 20230815
LR  - 20240210
IS  - 2473-4284 (Electronic)
IS  - 2473-4284 (Linking)
VI  - 7
DP  - 2023 Aug
TI  - Anaplastic Lymphoma Kinase Inhibitors for Therapy of Neuroblastoma in Adults.
PG  - e2300138
LID - 10.1200/PO.23.00138 [doi]
LID - e2300138
AB  - PURPOSE: Adult-onset neuroblastoma (AON) differs significantly in biology and 
      clinical behavior from childhood-onset disease. AON poses therapeutic challenges 
      since tolerance of intensive multimodality therapies that are standard of care 
      for pediatric neuroblastoma (NB) is poor. AON is enriched for somatic mutations 
      including anaplastic lymphoma kinase (ALK), deemed to be an oncogenic driver in 
      NB. ALK inhibitors (ALKis), therefore, have the potential to be of therapeutic 
      benefit. The purpose of this study is to report on their use in AON. METHODS: A 
      single-center retrospective review of adults with NB receiving ALKi (2012-2022) 
      was performed. Response was evaluated using International Neuroblastoma Response 
      Criteria. RESULTS: Fifteen patients with ALK-mutated AON were treated with US 
      Food and Drug Administration-approved ALKi starting at a median age of 34 (16-71) 
      years. Initial ALKi was lorlatinib, crizotinib, and alectinib in seven, five, and 
      three patients respectively; seven received multiple ALKis due to progressive 
      disease/intolerability of one agent. All patients experienced >/=grade 2 adverse 
      events (AEs): crizotinib and alectinib were associated primarily with 
      gastrointestinal AEs, lorlatinib with neurologic AEs, weight gain, and 
      hyperlipidemia resulting in dose reduction or discontinuation of ALKi in several 
      patients. No responses were observed with crizotinib (n = 5 patients), ceritinib, 
      alectinib, or brigatinib (n = 1 each). Of the 13 patients receiving lorlatinib, 
      four, five, and four patients had a complete or partial response (major response 
      rate 69%), and stable disease, respectively. Responses were noted in all disease 
      compartments; complete metabolic response was seen in two L2 patients. Ten of 13 
      patients remain progression-free at a median of 19 (6-50) months on lorlatinib. 
      Three (two receiving dose-reduced therapy) had progressive disease. Median 
      survival from start of first ALKi was 43 +/- 26 months. CONCLUSION: ALKis, 
      particularly lorlatinib, are effective treatment options for AON. However, AEs 
      necessitating dose reduction are common.
FAU - Stiefel, Jessica
AU  - Stiefel J
AUID- ORCID: 0000-0001-8393-4201
AD  - Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Kushner, Brian H
AU  - Kushner BH
AUID- ORCID: 0000-0002-8916-0697
AD  - Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Roberts, Stephen S
AU  - Roberts SS
AUID- ORCID: 0000-0001-8258-756X
AD  - Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Iglesias-Cardenas, Fiorella
AU  - Iglesias-Cardenas F
AUID- ORCID: 0000-0002-5563-1155
AD  - Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Kramer, Kim
AU  - Kramer K
AD  - Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Modak, Shakeel
AU  - Modak S
AUID- ORCID: 0000-0002-7280-1726
AD  - Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - JCO Precis Oncol
JT  - JCO precision oncology
JID - 101705370
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - 53AH36668S (Crizotinib)
RN  - 0 (Lactams, Macrocyclic)
RN  - OSP71S83EU (lorlatinib)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (ALK protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Humans
MH  - Middle Aged
MH  - Anaplastic Lymphoma Kinase/genetics
MH  - *Carcinoma, Non-Small-Cell Lung/genetics
MH  - Crizotinib/therapeutic use
MH  - Lactams, Macrocyclic/adverse effects
MH  - *Lung Neoplasms/genetics
MH  - *Neuroblastoma/drug therapy
MH  - Protein Kinase Inhibitors/adverse effects
MH  - Adolescent
MH  - Young Adult
PMC - PMC10581627
COIS- The following represents disclosure information provided by authors of this 
      manuscript. All relationships are considered compensated unless otherwise noted. 
      Relationships are self-held unless noted. I = Immediate Family Member, Inst = My 
      Institution. Relationships may not relate to the subject matter of this 
      manuscript. For more information about ASCO's conflict of interest policy, please 
      refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a 
      public database containing information reported by companies about payments made 
      to US-licensed physicians (Open Payments).
EDAT- 2023/08/10 18:42
MHDA- 2023/08/14 06:42
PMCR- 2024/08/10
CRDT- 2023/08/10 16:04
PHST- 2024/08/10 00:00 [pmc-release]
PHST- 2023/08/14 06:42 [medline]
PHST- 2023/08/10 18:42 [pubmed]
PHST- 2023/08/10 16:04 [entrez]
AID - PO.23.00138 [pii]
AID - 10.1200/PO.23.00138 [doi]
PST - ppublish
SO  - JCO Precis Oncol. 2023 Aug;7:e2300138. doi: 10.1200/PO.23.00138.