• Participants must have histologically or cytologically confirmed peripheral T cell lymphoma of one of the following subtypes: PTCL-NOS, Follicular helper T-cell lymphoma (ICC 2022) or Nodal T-follicular helper (TFH) cell lymphoma by (WHO 2022) which includes follicular helper T-cell lymphoma, AITL and follicular helper T cell lymphoma, follicular type, EATL, MEITL. All pathology will be reviewed at BWH. BWH review is not required prior to enrollment and patients may be enrolled based upon local pathology analysis. Ten blank slides will be required from outside tumor biopsy for correlative studies.

• No prior treatment for T NHL with the exception of one cycle of CHOP or CHOEP or 7 days of corticosteroids at a dose of up to prednisone 60 mg or equivalent for palliation of disease related symptoms so long as the corticosteroids are discontinued prior to tazemetostat prephase or cycle 1 of treatment if not receiving the prephase.

• At least one bi-dimensionally measurable lesion, defined as \>1.5 cm in its longest dimension as measured by CT.

• Age ≥18 years.

• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).

• Participants must have adequate organ and marrow function as defined below:

‣ absolute neutrophil count ≥1,000/mcL (750 mcl if bone marrow involvement with lymphoma)

⁃ platelets ≥75,000/mcL (25,000 if bone marrow involvement with lymphoma)

⁃ total bilirubin ≤ institutional upper limit of normal (ULN)

⁃ AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

⁃ creatinine ≤ 1.5 x institutional ULN OR

⁃ glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2

• Because the effects of tazemetostat on human immunodeficiency virus (HIV)-infected participants and anti-retroviral therapy is unknown, patients with known HIV infection are not eligible for this trial.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment, are not eligible.

• Left ventricular ejection fraction of \> 50% as assessed by echocardiography or multi-gate acquisition (MUGA) scan.

• The effects of tazemetostat on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. For women of childbearing potential, a negative serum pregnancy test result within 7 days prior to commencement of dosing. Women who are considered not to be of childbearing potential are not required to have a pregnancy test.

• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of tazemetostat administration.Women should use effective contraceptive methods beginning ≥28 days prior to initiating, during tazemetostat treatment, and for at least 6 months after the final dose of tazemetostat

• Ability to understand and the willingness to sign a written informed consent document.