Table 3.
Translational studies with immunotherapeutics targeting T and NK cells in the tumour microenvironment. Elo: elotuzumab; bort: bortezomib; dex: dexamethasone; thal: thalidomide; pom: pomalidomide; dara: daratumumab; CTD: cyclophosphamide, thalidomide, dexamethasone; NDMM: newly diagnosed multiple myeloma; RRMM: relapsed/refractory multiple myeloma.
| Target | Pre-clinical evidence | Phase 1/2 trials | Phase 3 trials |
|---|---|---|---|
| CD137 (4-1BB) | Vk*MYC[23, 124] | NCT02252263: Urelumab (+ elotuzumab) | |
| 5TGM1[123] | |||
|
| |||
| CS1 (SLAMF7) |
Anti-CS1, bortezomib (xenograft) [112] | Phase 1: Elo monotherapy[113] | NCT01335399 (ELOQUENT-1): Len/dex +/- elo in NDMM |
| Phase 1: Elo/bort[117] | |||
| Phase 2: Elo/bort/dex[118] | NCT01239797 (ELOQUENT-2): Len/dex +/- elo in RRMM[194] | ||
| Phase 1: Elo/len/dex[114] | |||
| Phase 1b/2: Elo/len/dex[115] | ACTRN12616001030460 (MM20): Elo/CTD vs CTD in RRMM | ||
| Phase 2: Elo/thal/dex[116] | |||
|
| |||
| CTLA-4 | CTLA-4 Ig (Vk*MYC)[23, 195] | NCT01592370 Arm 2: Ipilimumab (+ Nivolumab) | |
|
| |||
| KIR ligands | Anti-murine KIR mAb + len (xenograft)[120] | Phase 1: IPH2101 monotherapy[121] | |
| Phase 1: IPH2101 + len[122] | |||
| NCT02252263: Lirilumab (+ Elotuzumab) | |||
| NCT01592370 Arm 2: Lirilumab (+ Nivolumab) | |||
|
| |||
| PD-1 | PD-1 (Vk*MYC)[23] | Phase 1b: Nivolumab[134] | NCT02576977 (KEYNOTE 183): Pom/dex +/- |
| Pembrolizumab/len/dex in RRMM[196] | pembrolizumab in RRMM | ||
| Phase 1/2: Pembrolizumab/pom/dex[135] | |||
| NCT02579863 (KEYNOTE 185): Len/dex +/- | |||
| NCT01592370 Arm 3/4: Nivolumab + dara +/- pom/dex | pembrolizumab in NDMM | ||
| NCT02036502 (KEYNOTE-023): Phase 1 | |||
|
| |||
| PD-L1 | PD-L1 (5T33)[132, 140] | NCT02685826: Durvalumab/len +/-dex | |
| NCT02616640: Durvalumab/pom +/-dex | |||
| NCT02807454: Durvalumab +/-dara | |||
| NCT02431208: Atezolizumab +/-dara | |||