Evidence map›Paper›PMID 40551396›Full record

ArticlePediatric blood & cancer2025

Pulmonary Toxicity Associated With Concurrent Lorlatinib and Anti-GD2 Monoclonal Antibody Therapy in Patients With Neuroblastoma.

Wei Wei, Maggie Eidson Fader, Brian H Kushner, Fiorella Iglesias Cardenas, Kim Kramer, Ellen Basu, Shakeel Modak

Abstract read
In one paragraph

Article in Pediatric blood & cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Wei WeiDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID https://orcid.org/0000-0003-4391-6636
Maggie Eidson FaderDivision of Pediatric Hematology-Oncology, Nicklaus Children's Hospital, Miami, Florida, USA.
Brian H KushnerDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Fiorella Iglesias CardenasDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Kim KramerDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ellen BasuDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Shakeel ModakDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID https://orcid.org/0000-0002-7280-1726

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundThe anaplastic lymphoma kinase (ALK) inhibitor lorlatinib demonstrated safety without pulmonary toxicity in early-phase trials in patients with neuroblastoma. Lorlatinib is being tested with chemotherapy and immunotherapy in the Children's Oncology Group study ANBL1531. However, pulmonary toxicity was noted in patients receiving lorlatinib concurrently with anti-disialoganglioside 2 (GD2) monoclonal antibody (mAb) dinutuximab on the trial.

methodsAfter IRB approval, we performed a retrospective review on patients with neuroblastoma treated with lorlatinib and anti-GD2 mAbs from 9/2020 to 11/2024. Before 11/2023, lorlatinib was given concurrently with anti-GD2 mAbs; after 11/2023, it was withheld during mAb immunotherapy.

resultsTwenty-nine patients received lorlatinib with naxitamab (n = 12), dinutuximab (n = 11), or both (n = 6). Eight, 8, and 13 patients received lorlatinib with chemoimmunotherapy, mAbs, and both, respectively. Twenty of the 29 patients were treated with a total of 160 cycles before 11/2023, and 4 developed ≥grade 3 pulmonary toxicity. Severe respiratory failure with hemodynamic instability and the need for mechanical ventilation and extracorporeal membrane oxygenation occurred in two patients. The other two patients experienced hypoxia, wheezing, or cough, both managed with supportive care. All four recovered to <grade 3 toxicity. Three continued with lorlatinib alone or between cycles of mAbs without further >grade 2 pulmonary toxicities. Fifteen of the 29 patients were treated with 64 combined cycles after 11/2023, but none developed ≥grade 3 pulmonary toxicity.

conclusionsConcurrent use of lorlatinib with anti-GD2 mAbs may be associated with severe pulmonary toxicities. Temporarily withholding lorlatinib during immunotherapy appeared to mitigate this risk.

Indexed as

Antibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsGangliosidesLactams, MacrocyclicLung DiseasesNeuroblastomaAdolescentAminopyridinesChildChild, PreschoolFemaleFollow-Up StudiesHumansInfantLactamsMaleAminopyridinesAntibodies, Monoclonaldinutuximabganglioside, GD2GangliosidesLactamsLactams, MacrocycliclorlatinibPyrazolesanti‐GD2 mAblorlatinibpulmonary toxicity

Identifiers

PMID40551396
PMCPMC12558605

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.