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Home > Mechanism of Disease

Follicular lymphoma occurs
when B cells proliferate
without differentiating1,2,4,5

  • EZH2 is an epigenetic regulator of B-cell identity in the germinal center2
  • EZH2 represses the expression of gene sets that allow for germinal center exit and terminal differentiation2,3
  • EZH2 activity plays a role in both normal B-cell biology and in the pathogenesis of follicular lymphoma (FL)2
  • FL is caused by heterozygous combinations of oncogenic hits3,4

The degree to which FL relies on EZH2 activity depends on the complex interplay between multiple drivers of oncogenesis2,3

click here to view the image
↑ EZH2 activity Naive B cell GERMINAL CENTER Germinal center B cell

EZH2=enhancer of zeste homologue 2.

References: 1. Mamessier E, Broussais-Guillaumot F, Chetaille B, et al. Nature and importance of follicular lymphoma precursors. Haematologica. 2014;9(5):802-810. 2. Béguelin W, Popovic R, Teater M, et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013;23:677-692. 3. Huet S, Sujobert P, Salles G. From genetics to the clinic: A translational perspective on follicular lymphoma. Nat Rev Cancer. 2018;18:224-239. 4. Lackraj T, Goswami R, Kridel R. Pathogenesis of follicular lymphoma. Best Pract Res Cl Ha. 2018;31:2-14. 5. Naradikian MS, Scholz JL, Oropallo MA, Cancro MP. Understanding B cell biology. In: Bosch X, Ramos-Casals M, Khamashta MA (eds.). Drugs Targeting B-Cells in Autoimmune Diseases. Springer;2014.

Return to the TAZVERIK® (tazemetostat) 


Learn more about how EZH2 inhibition
works in FL.

Mechanism of Action


TAZVERIK is indicated for the treatment of:

  • 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.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


Warnings and Precautions

  • Secondary Malignancies

The risk of developing secondary malignancies is increased following treatment with TAZVERIK. Across clinical trials of 729 adults who received TAZVERIK 800 mg twice daily, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) occurred in 0.7% of patients. One pediatric patient developed T‑cell lymphoblastic lymphoma (T‑LBL). Monitor patients long‑term for the development of secondary malignancies.

  • Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, TAZVERIK can cause fetal harm when administered to pregnant women. There are no available data on TAZVERIK use in pregnant women to inform the drug-associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose-dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure (area under the plasma concentration time curve [AUC0‑45h]) at the 800 mg twice daily dose.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAZVERIK and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TAZVERIK and for 3 months after the final dose.

Adverse Reactions

In 99 clinical study patients with relapsed or refractory follicular lymphoma receiving TAZVERIK 800 mg twice daily: Serious adverse reactions occurred in 30% of patients who received TAZVERIK. Serious adverse reactions occurring in ≥2% were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia. The most common (≥20%) adverse reactions were fatigue (36%), upper respiratory tract infection (30%), musculoskeletal pain (22%), nausea (24%), and abdominal pain (20%).

Drug Interactions

Avoid coadministration of strong or moderate CYP3A inhibitors with TAZVERIK. If coadministration of moderate CYP3A inhibitors cannot be avoided, reduce TAZVERIK dose.

Avoid coadministration of moderate and strong CYP3A inducers with TAZVERIK, which may decrease the efficacy of TAZVERIK.

Coadministration of TAZVERIK with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and reduced efficacy of CYP3A substrates.


Because of the potential risk for serious adverse reactions from TAZVERIK in the breastfed child, advise women not to breastfeed during treatment with TAZVERIK and for one week after the final dose.

Before prescribing TAZVERIK, please read the full Prescribing Information.