The Lymphoma Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing you cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Phase II study update of tazemetostat in patients with relapsed/refractory follicular lymphoma

Jan 21, 2020

Patients with relapsed/refractory (R/R) follicular lymphoma (FL) represent a difficult-to-treat population, with limited treatment options. About 20% of FL patients have mutations in EZH2,1 an epigenetic regulator of gene expression and cell fate decision that is required for normal B cell biology.2 EZH2 biology is relevant in both mutant (MT) and wild-type (WT) EZH2 FL. Tazemetostat is a first-in-class, selective, oral EZH2 inhibitor, that has demonstrated antitumor activity in MT or WT EZH2 R/R FL patients, in a multicenter, open-label (NCT01897571) phase I/II study.3

The Lymphoma Hub has previously published an interim update from the phase II part of the study. At the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, Franck Morschhauser, CHRU Lille, Lille, FR, reported efficacy and safety data from the FL cohorts of the phase II study.4

Study design and patient characteristics4

  • Patients with FL (N= 99), aged ≥ 18 years, who had received ≥ 2 prior treatments (including at least one anti-CD20-based regimen), with a performance status of 0–2, and measurable disease, were prospectively assigned to cohorts according to EZH2 mutational status:
    • EZH2 MT cohort (n= 45)
    • EZH2 WT cohort (n= 54)
  • The median age was 62 (38─80) for MTEZH2 and 60.5 (36─87) for WT EZH2; the median number of prior therapies was two (1─11) for MT EZH2 and three (1─8) for WT EZH2
  • More patients who experienced disease progression within 24 months of diagnosis (POD24) were in the WTEZH2 cohort (59.3%) than in the MT EZH2 cohort (42.2%)
  • Tazemetostat was administered orally twice daily at a dose of 800 mg until progressive disease or withdrawal
  • The primary endpoint was objective response rate (ORR)
  • Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety


  • Data cuts: efficacy 9th August 2019 and safety 24th May 2019
  • The most frequent treatment-emergent adverse events (TEAEs) of grade ≥ 3 are represented by anemia (5%), thrombocytopenia (5%), asthenia (3%), fatigue (2%), abdominal pain (1%), and vomiting (1%)
  • Treatment-related TEAEs of grade ≥ 3 had a low rate, the most frequent included thrombocytopenia (3%), anemia (2%), asthenia (1%), and fatigue (1%)
  • Due to TEAEs:
    • Patients that discontinued treatment: 8%
    • Patients that had a dose reduction: 9%
    • Patients that had a dose interruption: 27% 
  • No treatment-related deaths were reported
  • Efficacy data, assessed by both independent radiology committee (IRC) and the investigator, are shown in Table 1
  • Evidence of tumor reduction (IRC assessed) was seen in 44/45 (98%) patients in the MTEZH2 cohort and 35/49 (71%) patients in the WT EZH2 cohort
  • The median overall survival (OS) was not reached in either cohort with a median follow-up of 22 months in the MT cohort and 35.9 months in the WT cohort
  • The ORR in high-risk subgroups:
    • Refractory to rituximab subgroup: 59% and 31% in MT and WTEZH2, respectively
    • POD24 subgroup: 63% and 25% in MT and WTEZH2, respectively
    • Refractory to prior treatment subgroup: 64% and 29% in MT and WTEZH2, respectively
  • There were eight patients (18%) in the MT EZH2 cohort and nine patients (17%) in the WT EZH2 cohort who continued on treatment after disease progression
Table 1. Study outcomes

CI, confidence interval; CR, complete response; DOR, duration of response; MT, mutant; NE, non-evaluable; NR, not reached; ORR, objective response rate; PR, partial response; PFS, progression-free survival; WT, wild-type.
aMedian DOR is still maturing for the MT EZH2 cohort



MT EZH2 (n= 45)

WT EZH2 (n= 45)





ORR, n (%)

(95% CI)

CR, n (%)

PR, n (%)

Stable disease, n (%)

Progressive disease, n (%)

35 (78)


4 (9)

31 (69)

10 (22)


31 (69)


6 (13)

25 (56)

13 (29)

1 (2)

18 (33)


3 (6)

15 (28)

16 (30)

16 (30)

19 (35)


2 (4)

17 (31)

18 (33)

12 (22)

Median time to first response, months










Median DORa, months

(95% CI)









Patients ongoing, n (%)

13 (29)


Median follow-up, months (range)

22 (2.8─43.5)

35.9 (0.3─48.8)

Median PFS, months

(95% CI)










  • Tazemetostat was generally well tolerated, with a low incidence of treatment-related TEAEs of grade ≥ 3 
  • Tazemetostat demonstrated clinically durable, single-agent activity in patients with R/R FL, including high-risk subgroups, and pronounced responses in patients with EZH2 mutations
  • Based on this data, a new drug application has been submitted to the US Food & Drug Administration (FDA) for accelerated approval of tazemetostat for the treatment of patients with R/R FL

Expert Opinion

  1. Bödör C. et al., EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood. 2013 Oct 31;122(18):3165-8. DOI: 10.1182/blood-2013-04-496893
  2. Béguelin W. et al., EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013 May 13;23(5):677-92. DOI: 10.1016/j.ccr.2013.04.011
  3. Italiano A. et al., Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol. 2018 May;19(5):649-659. DOI: 10.1016/S1470-2045(18)30145-1
  4. Morschhauser F. et al., Phase 2 Multicenter Study of Tazemetostat, an EZH2 Inhibitor, in Patients with Relapsed or Refractory Follicular Lymphoma; 2019 Dec 7. Oral Abstract #123: 61st American Society of Hematology (ASH) Annual Meeting & Exposition, Orlando, FL