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Table 2 Epigenetic therapies in past and ongoing trials open to FL patients

From: Evolving therapeutic landscape in follicular lymphoma: a look at emerging and investigational therapies

Treatment

Target

Publication/NCT#

Phase

Total n [FL]

Median lines of prior therapy

ORR%a [CR%]

Median PFS (mos)

Grade ≥ 3 AEs (%)b

Approved

EZH2 inhibitors

Tazemetostat

EZH2

[60]

II

99 [99; MT 45, WT 45)

2

MT: 69 [13] WT: 35 [4]

MT: 13.8 WT: 11.1

Nonec

 + 

Tazemetostat + rituximab

EZH2

NCT04762160

II

NAd

NAd

NAd

NAd

NAd

Tazemetostat + lenalidomide + rituximab

EZH2

NCT04224493

I

NAd

NAd

NAd

NAd

NAd

HDAC inhibitors

Vorinostat

Class 1 and 2 HDACs

[62]

II

50 [39]

1

49 [10]

20

Neutropenia [36], thrombocytopenia [23], lymphopenia [13], diarrhea [5], anorexia [7]

Vorinostat + rituximab

Class 1 and 2 HDACs

[64]

II

28 [22]

2

41 [27]

18.8

Lymphopenia [25], thrombocytopenia [18], neutropenia [11], fatigue [32], thrombosis [14], dehydration [11], hyperglycemia [11] hypotension [7], PNA [7],

Mocetinostat

HDAC 1,2,3,11

[66]

II

72 [31]

4

11 [4]

26.3

Fatigue [24], neutropenia [15], thrombocytopenia [12], anemia [8]

DNMT inhibitors

5-azacytidine + R-CHOP

DNMT1

[68]

I

10 [3]

3

66 [33]

NP

Neutropenia [50], thrombocytopenia [40], anemia [20], abscess [10], anorexia [10], bacteremia [10], nausea [10]

PRMT inhibitors

GSK3326595

PRMT5

NCT02783300e

I

NAd

NAd

NAd

NAd

NAd

JNJ-64619178

PRMT5

NCT03573310e

I

NAd

NAd

NAd

NAd

NAd

BET inhibitors

CPI-0610

BRD2, BRD4

[74]

I

44 [8]

4

12 [0]

NP

NP

  1. Abbreviations: AEs—adverse events; CR—complete response rate; MT—mutant EZH2; NP—not presented; ORR—overall response rate; PFS—progression-free survival; PNA—pneumonia; R-CHOP—rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone; WT—wild type EZH2
  2. aResponse rates in FL subset
  3. bGrade ≥ 3 seen in at least 5% of all patients regardless of lymphoma subtype
  4. cNo grade ≥ 3 events occurred in greater than 5% of patients, thrombocytopenia [3], neutropenia [3], anemia [2]
  5. dNot available, clinical trials are ongoing
  6. efirst in human study enrolling patients with NHL or solid tumors