Immunotherapeutics in Multiple Myeloma: How Can Translational Mouse Models Help?

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