Tazemetostat in the therapy of pediatric INI1-negative malignant rhabdoid tumors

Sci Rep. 2023 Dec 7;13(1):21623. doi: 10.1038/s41598-023-48774-2.

Abstract

Rhabdoid tumors are aggressive tumors that may arise in the kidney, soft tissue, central nervous system, or other organs. They are defined by SMARCB1 (INI1) or SMARCA4 alterations. Often, very young children are affected, and the prognosis is dismal. Four patients with primary atypical teratoid rhabdoid tumor (AT/RT, a rhabdoid tumor in the central nervous system) were treated by resection and high dose chemotherapy. Tazemetostat was introduced after completion of chemotherapy. Three patients have achieved an event free survival of 32, 34, and 30 months respectively. One progressed and died. His overall survival was 20 months. One patient was treated for a relapsed atypical teratoid rhabdoid tumor. The treatment combined metronomic therapy, radiotherapy, tazemetostat and immunotherapy. This patient died of disease progression, with an overall survival of 37 months. One patient was treated for a rhabdoid tumor of the ovary. Tazemetostat was given as maintenance after resection, chemotherapy, and radiotherapy, concomitantly with immunotherapy. Her event free survival is 44 months. Only approximately 40% of patients with rhabdoid tumors achieve long-term survival. Nearly all relapses occur within two years from diagnosis. The event free survival of four of the six patients in our cohort has exceeded this timepoint. Tazemetostat has been mostly tested as a single agent in the relapsed setting. We present promising results when applied as maintenance or add on in the first line treatment.

MeSH terms

  • Central Nervous System Neoplasms* / pathology
  • Child
  • Child, Preschool
  • DNA Helicases
  • Female
  • Humans
  • Infant
  • Neoplasm Recurrence, Local / drug therapy
  • Nuclear Proteins
  • Rhabdoid Tumor* / drug therapy
  • Rhabdoid Tumor* / pathology
  • SMARCB1 Protein
  • Teratoma* / pathology
  • Transcription Factors

Substances

  • tazemetostat
  • SMARCB1 Protein
  • SMARCA4 protein, human
  • DNA Helicases
  • Nuclear Proteins
  • Transcription Factors

Supplementary concepts

  • Typical Teratoid Rhabdoid Tumor