Severe adverse events during sirolimus "off-label" therapy for vascular anomalies.

Rössler, Jochen; Baselga, Eulalia; Davila, Victoria; Celis, Veronica; Diociaiuti, Andrea; El Hachem, Maya; Mestre, Sandrine; Haeberli, Dario; Prokop, Aram; Hanke, Christof; Loichinger, Wolfgang; Quéré, Isabelle; Baumgartner, Iris; Niemeyer, Charlotte M; Kapp, Friedrich G (2021). Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. (In Press). Pediatric blood & cancer, e28936. Wiley 10.1002/pbc.28936

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OBJECTIVES

Clinical studies have shown low toxicity and a favorable safety profile for sirolimus in vascular anomalies. Here, we describe severe adverse events (SAEs) observed during "off-label use" for vascular anomalies.

METHODS

We performed a retrospective, multicenter chart review for SAEs during "off-label" sirolimus therapy for vascular anomalies and analyzed these cases by a predesigned workflow.

RESULTS

We identified 17 SAEs in 14 patients diagnosed with generalized lymphatic anomaly (n = 4), Gorham-Stout disease (n = 2), central conducting lymphatic anomaly (n = 1), lymphatic malformation (n = 4), tufted angioma (n = 1), kaposiform hemangioendothelioma (n = 1), and venous malformation in a patient with CLOVES syndrome (n = 1). Three patients presented two SAEs each. The age at initiation of sirolimus therapy was under 2 years (n = 5), 2-6 years (n = 5), and older than 12 years (n = 4). SAEs occurred during the first 3 months of sirolimus therapy (n = 7), between 3 and 12 months (n = 7) and after 1 year of therapy (n = 3). The most frequent SAE was viral pneumonia (n = 8) resulting in one death due to a metapneumovirus infection in a 3 months old and a generalized adenovirus infection in a 28-month-old child. Sirolimus blood level at the time of SAEs ranged between 2.7 and 21 ng/L. Five patients were on antibiotic prophylaxis.

CONCLUSIONS

Most SAEs are observed in the first year of sirolimus therapy; however, SAEs can also occur after a longer treatment period. SAEs are potentially life threatening, especially in early infancy. Presence of other risk factors, that is, underlying vascular anomaly or immune status, may contribute to the risk of SAEs. Sirolimus is an important therapeutic option for vascular anomalies, but patients and physicians need to be aware that adequate monitoring is necessary, especially in patients with complex lymphatic anomalies that are overrepresented in our cohort of SAEs.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Haematology/Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)

UniBE Contributor:

Rössler, Jochen Karl and Häberli, Dario

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1545-5009

Publisher:

Wiley

Language:

English

Submitter:

Jochen Karl Rössler

Date Deposited:

29 Apr 2021 09:18

Last Modified:

30 Apr 2021 01:34

Publisher DOI:

10.1002/pbc.28936

PubMed ID:

33580918

Uncontrolled Keywords:

severe adverse events sirolimus toxicity vascular anomalies

BORIS DOI:

10.48350/154476

URI:

https://boris.unibe.ch/id/eprint/154476

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