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

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

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	None^c	+
Tazemetostat + rituximab	EZH2	NCT04762160	II	NA^d	NA^d	NA^d	NA^d	NA^d	–
Tazemetostat + lenalidomide + rituximab	EZH2	NCT04224493	I	NA^d	NA^d	NA^d	NA^d	NA^d	–
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	NCT02783300^e	I	NA^d	NA^d	NA^d	NA^d	NA^d	–
JNJ-64619178	PRMT5	NCT03573310^e	I	NA^d	NA^d	NA^d	NA^d	NA^d	–
BET inhibitors
CPI-0610	BRD2, BRD4	[74]	I	44 [8]	4	12 [0]	NP	NP	–

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
^aResponse rates in FL subset
^bGrade ≥ 3 seen in at least 5% of all patients regardless of lymphoma subtype
^cNo grade ≥ 3 events occurred in greater than 5% of patients, thrombocytopenia [3], neutropenia [3], anemia [2]
^dNot available, clinical trials are ongoing
^efirst in human study enrolling patients with NHL or solid tumors

ISSN: 1756-8722