Targeted Therapy with Sirolimus and Nivolumab in a Child with Refractory Multifocal Anaplastic Ependymoma

Abstract

Pediatric ependymoma (EPN) is the third most common central nervous system (CNS) tumor, with 90% arising intracranially. Management typically involves maximal surgical resection and radiotherapy, but patients’ outcome is poor. Moreover, there are only a few therapeutical options available for recurrent or refractory disease. In this report, we present the case of a 7-year-old girl with relapsed refractory multifocal grade III EPN who failed conventional treatments and experienced a stable and durable response to the immune checkpoint inhibitor (ICPI) nivolumab in association with the mammalian target of rapamycin (m-TOR) inhibitor sirolimus. This experimental therapy was targeted on immune phenotypical analyses of the patient’s last relapse tumor sample, and this procedure should be routinely done to find new possible therapeutical approaches in recurrent solid tumors.

The Role of Immunotherapy in the Treatment of Rare Central Nervous System Tumors

“…PD-L1 expression was seen on 0% of tumor cells and 5% of tumor-infiltrating immune cells, indicating that the response to ICI treatment was independent of PD-L1 expression [ 69 ]. One pediatric patient with recurrent RELA-fusion, PD-L1+ (20%) ependymoma was treated with nivolumab and sirolimus and had stable disease for 1 year after the initiation of immunotherapy [ 70 ]. Another patient with spinal ependymoma treated with ipilimumab and nivolumab for 18.6 months had stable disease [ 71 ].…”

Molecular Stratification of Childhood Ependymomas as a Basis for Personalized Diagnostics and Treatment

“…Specific expression of PD-L1 on both tumor and myeloid cells in ST-EPN-RELA has been demonstrated, accompanied by high levels of PD-1 expressed by tumor-infiltrating T cells (both CD4 and CD8) [93,94]. In the context of immunotherapy, ST-EPN-RELA progression may be controlled with PD-1 inhibitors, such as pembroluzimab or nivolumab [95].…”