Table 1.
Clinical evaluation of immune checkpoint-based therapies blockade for the treatment of B-cell lymphomas.
| Targets | Drug/Regimen | Trial ID | Phase | N | Disease | Response | DOR/PFS/OS | Ref |
|---|---|---|---|---|---|---|---|---|
| PD-L1 CD20 |
Atezolizumab + Obinutuzumab + Bendamustine/ Atezolizumab + Obinutuzumab + CHOP |
NCT02596971 | 1/2 | 40 | FL, DLBCL | ORR = 95% CR = 75% |
PFS = 74.9% OS = 86.4% (24-month) |
[121] |
| PD-L1 CD20 |
Atezolizumab + Obinutuzumab + Lenalidomide |
NCT02631577 | 1/2 | 20 | FL | ORR = 85% CR = 80% |
14.5 months | [122] |
| PD-L1 CD20 EZH2 |
Atezolizumab + Obinutuzumab/ Atezolizumab + Tazemetostat |
NCT02220842 | 1 | 43 | FL, DLBCL | ORR = 16% CR = 5% |
PFS = 1.90 months | [123] |
| PD-L1 CD20 BCL2 |
Atezolizumab + Obinutuzumab + Venetoclax |
NCT03276468 | 2 | 58 | DLBCL | ORR = 23.6% | N/A | [124] |
| PD-L1 | Mosunetuzumab/ Atezolizumab + Mosunetuzumab |
NCT02500407 | 1 | 218 | FL, DLBCL, t-FL, iNHL |
ORR = 64.1% (iNHL)/34.7% (others) CR = 42.2% (iNHL)/18.6% (others) |
92.6% (5.8 months, iNHL) 68.2% (8.8 months, aNHL) |
[125] |
| PD-L1 | Atezolizumab + CD20-TCB (RG6026) |
NCT03533283 | 1 | 36 | FL, DLBCL, MCL, PMBL, LPL, iNHL | ORR = 36% CR = 17% |
N/A | [126] |
| PD-L1 | Atezolizumab + KTE-C19 (Axi-cel) |
NCT02926833 | 1/2 | 28 | DLBCL | ORR = 75% CR = 46% |
not reached | [127] |
| PD-L1 BTK |
Durvalumab + Ibrutinib |
NCT02401048 | 1/2 | 61 | FL, DLBCL | ORR = 25% | PFS = 4.6 months OS = 18.1 months |
[120] |
| PD-L1 | Durvalumab + R-CHOP |
NCT03003520 | 2 | 46 | DLBCL | CR = 54.1% | PFS = 12 months | [128] |
| PD-L1 | Durvalumab + JCAR014 |
NCT02706405 | 1 | 13 | DLBCL LBCL HG-BCL |
ORR = 50% CR = 42% |
N/A | [129] |
| PD-1 | Pembrolizumab | NCT01953692 | 1b | 31 | DLBCL, FL, PMBL, cHL, MM | ORR = 58.1% CR = 19.4% PR = 38.7% SD = 22.6% PD = 19.4% |
DOR: not reached PFS = 11.4 months |
[130] |
| PD-1 | Pembrolizumab | NCT02650999 | 1/2 | 12 | DLBCL, FL, MCL, PMBL | ORR = 27% CR = 9% PR = 18% SD = 9% PD = 64% |
N/A | [131] |
| PD-1 | Nivolumab | NCT02038933 | 2 | 121 | DLBCL, B-NHL | ORR = 18% CR = 5% PR = 14% SD = 14% PD = 49% |
DOR = 7.4 months | [7] |
| PD-1 | Nivolumab | NCT02038946 | 2 | 116 | FL | ORR = 4% | DOR = 114 months | [68] |
| PD-1 | Pembrolizumab + ASCT |
NCT02362997 | 2 | 31 | DLBCL, PMBL, iNHL | CR = 59% | OS = 93% PFS = 58% |
[102] |
| PD-1 CD20 |
Nivolumab + Rituximab |
NCT03245021 | 1 | 19 | FL, B-NHL | ORR = 84% CR = 47% PR = 37% PR = 5% SD = 11% |
N/A | [132] |
| PD-1 | Pembrolizumab + R-CHOP |
NCT02541565 | 1 | 33 | DLBCL, FL | ORR = 90% CR = 77% |
PFS = 83% (2-year) |
[133] |
| PD-1 TLR4 CD20 |
Pembrolizumab + G100 + Rituximab |
NCT02501473 (Discontinued) |
1/2 | 18 | FL, MZL | ORR = 33.3% PR = 33.3% SD = 61.1% PD = 5.6% |
N/A | N/A |
| PD-1 | Pembrolizumab + cyclophosph. + DPX-Survivac |
NCT03349450 | 1 | 17 | DLBCL | 2 CR, 2 PR, 2 SD | N/A | [134] |
| PD-1 BTK |
Nivolumab + Ibrutinib |
NCT02329847 | 1/2 | 144 | DLBCL, FL, CLL-RT, SLL | CR = 61% PR = 14% SD = 3% |
N/A | [135] |
| PD-1 BTK |
Pembrolizumab + Acalabrutinib |
NCT02362035 | 1/2 | 61 | DLBCL, cHL, CLL, MM, WM | ORR = 26% CR = 7% PR = 20% SD = 30% PD = 36% |
PFS = 1.9 months | [136] |
| PD-1 BTK PI3K |
Pembrolizumab + Ibrutinib + Idelalisib |
NCT02332980 | 2 | 29 | FL, CLL, CLL-RT, MZL, RT, WM, SLL | ORR = 17% CR = 3% PR = 7% |
N/A | [104] |
| PD-1 CDK |
Pembrolizumab + Dinaciclib |
NCT02684617 | 1 | 128 | DLBCL, FL, CLL, MM | ORR = 18% 3 CR, 4 PR |
DOR = 4.9 months PFS = 2.1 months |
[137] |
| PD-1 HDAC |
Pembrolizumab + Vorinostat |
NCT03150329 | 1 | 30 | DLBCL, PMBL, FL, cHL | ORR = 30% CR = 30% |
DOR = 6 months PFS = 59% |
[138] |
| PD-1 HDAC |
Pembrolizumab + Entinostat |
NCT03179930 | 2 | 22 | FL, cHL | ORR = 92% | N/A | [139] |
| PD-1 | Nivolumab + Lenalidomide |
NCT03015896 | 1/2 | 10 | DLBCL, FL, MCL, MZL, WM, cHL | 1 CR, 2 PR, 3 PD | N/A | [138] |
| PD-1 CD30 |
Nivolumab + Brentuximab vedotin |
NCT02581631 | 1/2 | 30 | DLBCL, PMBL, PTCL, CTCL, MF, SS | ORR = 73% CR = 37% SD = 10% PD = 10% |
DOR = not reached PFS = 63.5% (6 months) |
[106] |
| PD-1 CD19 CD22 |
Pembrolizumab + AUTO3 |
NCT03287817 | 1/2 | 24 | DLBCL, t-FL, PMBL | ORR = 75% CR = 63% |
N/A | [140] |
| PD-1 CD19 |
Pembrolizumab + Tisagenlecleucel |
NCT03630159 | 1 | 8 | DLBCL | 1 PR 2 PD |
N/A | [141] |
| PD-1 CTLA-4 | Nivolumab + Ipilimumab |
NCT01592370 | 1/2 | 169 | cHL, B-NHL, T-NHL, MM | ORR = 20% PR = 20% SD = 7% |
DOR = not reached PFS = not reached OS = not reached |
[142] |
| CTLA-4 | Ipilimumab | NCT00089076 | 1/2 | 18 | DLBCL, FL, MCL | 1 CR, 1 PR | N/A | [143] |
| CTLA-4 CD20 |
Ipilimumab + Rituximab |
NCT01729806 | 1 | 33 | DLBCL, FL, MCL | ORR = 24% | PFS = 2.6 months, FL = 5.6 months | [144] |
| CTLA-4 PD-1 |
Ipilimumab + Nivolumab |
NCT01822509 | 1 | 28 | B-NHL | ORR = 32% | PFS = 1 year | [145] |
| CTLA-4 | Ipilimumab + Lenalidomide |
NCT01919619 | 2 | 11 | DLBCL, FL, MCL | ORR = 73% | 4.6–12 months | [146] |
| CD47 CD20 |
Hu5F9-G4 + Rituximab |
NCT02953509 | 1b/2 | 115 | DLBCL, iNHL | ORR = 36% (DLBCL)/61% (iNHL) CR = 15% (DLBCL)/24% (iNHL) SD = 12% (DLBCL)/24% (iNHL) |
N/A | [147] |
| CD47 CD20 |
TTI-621 + Rituximab |
NCT02663518 | 1 | 32 | DLBCL | ORR = 29% CR = 14% (monotherapy) ORR = 24% CR= 4% (combination) |
N/A | [148] |
| CD47 CD38 |
TTI-622 + Daratumumab |
NCT03530683 | 1 | 19 | DLBCL, MCL, FL | CR = 10% PR = 10% |
N/A | [149] |
| CD47 CD20 |
ALX148 + Rituximab |
NCT03013218 | 1 | 33 | DLCBL, MCL, FL, MZL | ORR = 41%/62.5% CR = 9%/11% |
N/A | [150,151] |
| CD40 | Dacetuzumab | NCT00103779 | 1 | 50 | DLBCL, MCL, FL, MZL | CR = 2% PR = 10% SD = 26% |
N/A | [152] |
| CD40 | Dacetuzumab | NCT00435916 | 2 | 46 | Relapsed FL, DLBCL, MZL |
ORR = 9% CR = 4% PR = 4% 28% SD |
N/A | [153] |
| CD40 | Lucatumumab | NCT00670592 | 1/2 | 111 (74) | FL, MZL, MCL, DLBCL | 33% OR 5% CR 29% PR 52% SD |
N/A | [154] |
| CD40 CD20 |
Dacetuzumab + Rituximab + chemotherapy |
NCT00655837 | 1 | 30 | DLBCL | ORR = 47% CR = 20% PR = 27% |
PFS = 25 weeks | [155] |
| CD40 CD20 |
Dacetuzumab Rituximab + chemotherapy |
NCT00529503 | 2 | 154 (101) | DLBCL, FL | 67% OR 18% SD 33% CR 33% PR |
not reached | [156] |
| CD27 | Varlilumab | NCT01460134 | 1 | 90 (18) | MCL, MZL, DLBCL, CLL, cHL, TCL | SD = 16% | DOR = 6% (14-month) | [157] |
| CD80 CD20 |
Galiximab + Rituximab | NCT00363636 | 3 | 337 | FL | 51% | 12 months | [158] |
| CD80 | Galiximab | NCT00575068 | 1/2 | 38 | FL | ORR = 63% | PFS = 11.7 months | [159] |
| CD80 CD20 |
Galiximab + Rituximab |
NCT00048555 | 1/2 | 73 | FL | ORR = 62% | 11.7 months | [160] |
| CD80 CD20 |
Galiximab + Rituximab |
NCT00117975 | 2 | 61 | FL | 72.1% | 2.9 years | [160] |
| 4-1BB | Urelumab | NCT01471210 | 1 | 60 | DLBCL, FL, B-NHL | ORR = 6% (DLBCL)/12% (FL)/17% (others) | PFS = 8.1 weeks (DLBCL)/8.9 weeks (FL)/13.4 weeks (others) | [161] |
| 4-1BB CD20 |
Urelumab + Rituximab |
NCT01775631 | 1 | 46 | DLBCL, FL |
ORR = 10% (DLBCL)/35% (FL) | PFS = 9 weeks (DLBCL)/40.4 weeks (FL) | [161] |
| 4-1BB CD20 |
Utomilumab + Rituximab |
NCT01307267 | 1 | 67 | FL, MCL, DLBCL | ORR = 21 | PFS = 4.6 months | [162] |
| CD70 | SGN-CD70A |
NCT02216890 Terminated |
1 | 38 | DLBCL, FL, MCL | PR = 15% SD = 30% |
PFS = 1.9 months | [163] |
Abbreviations: FL, follicular lymphoma; t-FL, transformed follicular lymphoma; DLBCL, diffuse large B-cell lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; B-NHL, B-cell non-Hodgkin lymphoma; iNHL, indolent B-cell non-Hodgkin lymphoma; aNHL, aggressive B-cell non-Hodgkin lymphoma; LBCL, large B-cell lymphoma; HG-BCL, high-grade B-cell lymphoma; cHL, classical Hodgkin lymphoma; CLL-RT, chronic lymphocytic leukaemia Richter transformation; PMBL, primary mediastinal B-cell lymphoma; PTCL, peripheral T-cell lymphoma; CTCL, cutaneous T-cell lymphoma; MF, myelofibrosis; SS, Sezary syndrome; MM, multiple myeloma; ORR, overall response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; DOR, duration of response; PFS, progression-free survival; OS, overall survival; NA, not available.