Table 3 Experimental combinations in the front-line setting

Alemtuzumab

Phase II [23]

T-PLL

32

IV route: 91, 81 SubQ route: 33

67% at 12 months

37% at 48 months

IV route: 2 patients with grade 4 hematologic AEs; 2 asymptomatic CMV reactivation; 2 skin reactionsSubQ route: 22% of patients died on treatment

Alemtuzumab + CHOP, “CHOP-C”

GITIL phase II [71]

PTCL, PTCL-NOS 58.3%, AITL 25%

ALCL, ALK− 12.5%

24

75, 71

48% at 2 years

53% at 2 years

JC viral encephalitis in 1 pt

Invasive aspergillosis in 2 pts PJP in 1 pt

Staphylococcus sepsis in 1 pt

CHOP ± alemtuzumab followed by ASCT

ACT-1 phase III [89]

CD 52+ PTCL (no ALCL), PTCL-NOS 58%, AITL 21%

65

77, 52

37% at 3 years

52% at 3 years

Grade 4 leukopenia (73% vs 35% in CHOP arm, p = 0.001)

Grade ≥ 3 bacterial/fungal infections and other serious AEs similar in both arms

*After 2pts developed systemic fungal infections, an amendment tapered ALZ dose from 360 mg (30 mg on days 1 + 2 of each CHOP course) to 120 mg (30 mg on day 1 of CHOP courses 1–4)

Alemtuzumab + CHOP-14

HOVON phase II [72]

CD 52 + PTCL, PTCL-NOS 50%, AITL 30%, subcutaneous panniculitis-like (SPTCL) 15%, EATL 5%

20

90, 60

10

27

Neutropenic fever (40%), CMV reactivation (35%), secondary EBV-related lymphoma (15%)

Alemtuzumab + DA-EPOCH

NCI phase I/II [73]

CD 52+ PTCL, PTC

-NOS 35%,ATLL 32%, AITL 13%,CGDTCL 6%,epatosplenic TCL 6%

30

83.3, 57

6.6

20.2

5 treatment-related deaths:

2 sepsis, 1 cardiac arrest, 1 pneumonia, 1 disseminated toxoplasmosis

Romidepsin + CHOP, “Ro-CHOP”, LYSARC

LYSA phase I/II [90]

PTCL, PTCL-NOS 28%, AITL 22%

ALCL, ALK− 11%, EATL 6%, follicular PTCL 6%, ATLL 6%

37

69, 51

41% at 30 months

71% at 30 months

Gr ≥ 3 AEs: neutropenia (89%), thrombocytopenia 78%), anemia (43%)

QT prolongation < 480 ms (37%); 480–500 ms (5%)

Lenalidomide + CHOP, “len-CHOP”

LYSA phase II [77]

AITL, pts > 59 years old

78

47.4,43.6

42.3% at 2 years

60.1% at 2 years

29% discontinuation rate due to toxicities (15 pts) or POD (8 pts)

4 secondary malignancies

5 treatment-related deaths (4 infections)

Lenalidomide + CHOEP, “len-CHOEP”

T cell consortium phase II [76]

PTCL, PTCL-NOS 57.5%,

AITL 30%

ALCL, ALK− 12.5%

12

68,48

68% at 1 year

89% at 1 year

25% discontinuation rate due to toxicity (6pts) or POD (4pts)

5 deaths: 1 POD, 2 sepsis, 1 cardiac arrest, 1 secondary malignancy (AML)

Belinostat + CHOP

Bel-CHOP phase I [74]

PTCL, PTCL-NOS 43%, ATIL 39%

ALCL, ALK+ 9%

ALCL, ALK− 4%

23

89, 72

Not reported

Not reported

Gr ≥ 3 AEs: neutropenia (26%), anemia (22%), lymphopenia (17%)

Pralatrexate alternating with CEOP

T cell Consortium phase II [78]

PTCL,PTCL-NOS 64%, AITL 24%

ALC, ALK− 12%

33

70, 52

39% at 2 years

60% at 2 years

Gr ≥ 3 AEs: anemia (27%), thrombocytopenia (12%), febrile neutropenia (18%), mucositis (18%), sepsis (15%), elevated creatinine (12%), elevated and liver transaminases (12%)

Chidamide + CHOP

Phase Ib/II [75]

PTCL

,PTCL-NOS 40%, AITL 26.7%

ALCL, ALK+ 13.3%

ALCL, ALK− 10%

30

82.1, 46.4

14,54.3% at 12 months

Not reached,100% at 12 months

Gr ≥ 3 AEs: leukopenia (90%), neutropenia (83.3%), lymphopenia (40%), vomiting (13.3%), thrombocytopenia (10%), and febrile neutropenia (10%)