Tazemetostat — Drug Monograph

Brand names: Tazverik

Drug class: Other

Mechanism of Action

Tazemetostat is a small-molecule inhibitor of EZH2 (Enhancer of Zeste Homolog 2) histone methyltransferase. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) which methylates Histone H3 Lysine 27 (H3K27me3), leading to transcriptional silencing of genes involved in cell cycle inhibition and differentiation. Tazemetostat blocks this methylation, thereby restoring the expression of tumor suppressor genes. This is particularly effective in tumors lacking the SNF5/INI1 subunit (SMARCB1), which normally antagonizes EZH2.

FDA Indications

• Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection
• Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies
• Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options

Common Side Effects

• Fatigue
• Nausea
• Abdominal pain
• Constipation
• Decreased appetite
• Upper respiratory tract infection
• Vomiting
• Diarrhea

Clinical Pearl

Tazemetostat represents a unique "epigenetic" targeted therapy. In follicular lymphoma, it has activity regardless of EZH2 mutation status, though response rates are higher in mutated patients. Be vigilant for the development of secondary malignancies, particularly T-cell lymphomas, which have been reported in clinical trials. It is generally well-tolerated compared to traditional cytotoxic salvage regimens for sarcoma. Advise patients to avoid grapefruit and Seville oranges due to CYP3A…

Related Therapies & Mechanisms

• Axicabtagene ciloleucel (Yescarta) — Other · Lymphoma
• Belinostat (Beleodaq) — Other · Lymphoma
• Bleomycin (Blenoxane) — Other · Lymphoma
• Brexucabtagene autoleucel (Tecartus) — Other · Lymphoma