Sirolimus has been used in a number of studies as an experimental drug for the treatment of vascular malformations. Especially for patients with lymphatic and vascular malformations it seems to have a beneficial effect. Although the drug is generally safe, some patients are more susceptible to complications. In a retrospective study*, researchers looked at the complications that occurred when treating vascular malformations with sirolimus.
The researchers looked at the treatment of patients from 7 different clinics (total of 113 patients). In 14 patients, 17 severe adverse events (SAEs) developed. Most SAEs occurred during 3-12 months of treatment.
The most frequent SAE (in eight of the 17 cases (47%)), was a respiratory infection requiring hospitalisation and oxygen therapy. In five of these respiratory SAEs, the infectious agent could be identified. They were different types of viruses ranging from rhinovirus to pneumococcus. All but three patients recovered fully after 3-15 days. Two patients died.
The type of underlying vascular malformation seems to be important in the development of specific SAEs; for example, in GSD (Gorham-Stout disease), osteosynthetic material (plate, pin or screws used to fix broken bones) or some other foreign object can easily become infected. The underlying vascular anomaly may also be a risk factor for the occurrence of an SAE. For example, involvement of lungs and/or intestines and spleen can be influencing factors for serious infections.
It cannot be excluded that the deceased patients already suffered from an underlying immunodeficiency that made them more susceptible to serious infections. One of the deceased patients had been receiving penicillin for a year.
It is therefore very important to continue to monitor the patients closely. Further clinical studies are required to determine the safety profile of sirolimus, the incidence of SAEs in different patient populations and the optimal treatment/dose.
*Severe adverse events during sirolimus “off-label” therapy for vascular anomalies. J. Rössler et al., Pediatr Blood Cancer. 2021;e28936. https://doi.org/10.1002/pbc.28936
**An SAE is a severe adverse event in a patient or subject that does not necessarily have a causal relationship with treatment and is:
- is fatal, and/or
- poses a life-threatening risk to the subject, and/or
- necessitates admission to hospital or prolongation of existing hospitalisation, and/or
- causes permanent or significant disability or incapacity, and/or
- is a congenital anomaly or malformation, and/or
- could, in the opinion of the person conducting the scientific research, have developed into a serious adverse event, but this serious adverse event did not occur as a result of intervention.
Source: CMTC.nl, written by Dr. Lilian Vermeer