Table 1 Licensed agents in PTCL

Frontline

Brentuximab vedotin + CHP, “BV-CHP”

Anti-CD30 Ab-drug conjugate

ECHELON-2 multinational phase III [70]

BV-CHP vs. CHOP

CD30+ PTCL, ALCL 72% (ALK+22%, ALK− 50%), PTCL-NOS 13%, AITL 13%

226

83, 68

Not reported

48.2

Not reached after 3 years follow-up, 34% risk of death reduction

Increased diarrhea, any grade (38% vs 20%) in BV-CHP vs CHOP, other AEs comparable between two cohorts

Relapsed/refractory

Brentuximab vedotin

Anti-CD30 Ab-drug conjugate

Multinational phase II [15]

ALCL, ALK+ 28%, ALK− 72%

58

86, 57

12.6

20, 57% at 5 years

Not reached,79% at 5 years

Grade ≥ 3 AEs: neutropenia (21%), thrombocytopenia (14%), peripheral sensory neuropathy (12%)

Multinational phase II [16]

CD30+ PTCL, PTCL-NOS 63%, AITL 37%

35

41, 24

7.6

2.6

Not reported

Grade ≥ 3 AEs: neutropenia (14%), peripheral sensory neuropathy (9%), and hyperkalemia (9%)

Romidepsin

HDAC-1 inhibitor

Multinational phase II [30]

PTCL, PTCL-NOS 53%, AITL 21%, ALCL, ALK− 16%

130

25, 15

28

4

11.3

Grade ≥ 3 AEs: thrombocytopenia (24%), neutropenia (20%), infections (all types, 19%)

Belinostat

Pan-HDAC inhibitor

BELIEF multinational phase II [35]

PTCL, PTCL-NOS 64%, ATIL 18%, ALCL 14% (ALK+ 2%, ALK− 12%), EATL 2%, ENKTL 2%, HSTCL 2%

129

25.8,10.8

13.6

1.6

7.9

Grade ≥ 3 AEs: anemia (10.8%), thrombocytopenia (7%), dyspnea (6.2%), neutropenia (6.2%)

Chidamide*

HDAC class I/II inhibitor

Chinese phase II [36]

PTCL, PTCL-NOS 35%, ALCL 22% (ALK− 14% ALK+ 4%, ALK unk. 4%), NKTCL 20%, AITL 13%

79

28, 14

9.9

2.1

21.4

Grade ≥ 3 AEs: thrombocytopenia (22%), leukopenia (13%), neutropenia (11%)

Pralaxtrexate

Antifolate

PROPEL North American phase II [66]

PTCL

109

29, 11

10.5

3.5

14.5

Grade ≥ 3 AEs: thrombocytopenia (32%), mucositis (22%), neutropenia (22%), anemia (18%)

Mogamulizumab^¥

Anti-CCR4 mAb

Japanese phase II [27]

CCR4+ R/R ATLL, acute 54%, lymphomatous 23%, chronic 23%

26

50, 31

Not reported

5.2

14.4, 23% at 3 years

All grades: infusion reactions (89%) skin rash (63%, 1 Stevens-Johnson syndrome)

Skin rash appears to correlated with response

Japanese phase II [86]

CCR4+ (≥ 10% by IHC), relapsed PTCL (no refractory pts), PTCL-NOS 55%, AITL 41%, ALCL, ALK− 3%

29

34, 13.5

Not reported

2

14.2

Grade ≥ 3 AEs: lymphopenia (81%), neutropenia (38%), leukopenia (43%)

Skin rash (all grades), 51%; grade ≥ 3, 11%