Table 2. . Nonsurface receptor antibodies in relapsed refractory multiple myeloma.
| Study (year) study design | Number of patients | Antibody | Target | Median prior therapies | Dose | Number of cycles | Regimen | Outcome | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| Suzuki et al. (2015) Phase I | 9 | Siltuximab | IL-6 | 1–2 | 5.5/11 mg/kg | ≥9 | Siltuximab + Bor (1.3 mg/m2)+ Dex (20 mg) | CR = 22%; PR = 44% | [38] |
| Orlowski et al. (2015) Phase II | 142 | Siltuximab + Bor | IL-6 | 1–3 | Siltuximab 6 mg/kg | 4 | MoAb + Bor | mPFS = 8 m; ORR = 55%; CR = 11%; OS = 30.8 m | [36] |
| 139 | Bor + placebo | Placebo + Bor | mPFS = 7.6; ORR = 47%; CR = 7%; OS = 36.8 m | ||||||
| Voorhees et al. (2009) Phase II | 14 | Siltuximab | IL-6 | 4 | 6 mg/kg | 4 | MoAb monotherapy | No response (CR/PR); SD = 62%; PD = 39% | [37] |
| 39 | Siltuximab + Dex | 6 mg/kg + 40 g | Siltuximab + Dex | ORR = 23%; PR = 17%; MR = 6%; SD = 57%; PD = 17%; PFS = 3.7 m | |||||
| Raje et al. (2017) Phase II | 74 | Tabalumab | BAFF | 1–3 | 100 mg | 8 or 10 | Tab + Bor + Dex | ORR = 58.1% | [41] |
| 74 | Tabalumab | 300 mg | Tab + Bor + Dex | ORR = 59.5% | |||||
| 72 | Placebo | No MoAb | Placebo + Bor + Dex | ORR = 61.6% | |||||
| Iida et al. (2016) Phase I | 16 | Tabalumab | BAFF | 1–5 | 100–300 mg | ≥9 | Tab + Bor (1.3 mg/m2) + Dex (20 mg/day) | ORR = 56.3%; CR = 0%; VGPR = 18.8%; SD = 1.3%; PD = 18.8% | [42] |
| Rossi et al. (2009) Phase I | 12 (11 REP) | Atacicept | BAFF | NR | 2–10 mg/kg | 5 | MoAb monotherapy | No ORR; PD = 54%; SD = 45% | [43] |
| White et al. (2013) Phase II | 49 | Bevacizumab + Bor | VEGF | 1–3 | Bevacizumab 15 mg/kg iv. | 8 | MoAb + Bor | ORR = 51%; PR = 16.3%; mPFS = 6.2 m | [44] |
| 53 | Bor + placebo | Bor 1.3 mg/m2 | Placebo + Bor | ORR = 43.4%; PR = 7.5%; mPFS = 5.1 m | |||||
| Somlo et al. (2011) Phase II | 6 | Bevacizumab | VEGF-A | 3 (0–5) | Bevacizumab 10 mg/kg | 4 | Monotherapy | PD = 29–69 days; SD = 238 days; SD = 16.6%; PD = 83% | [45] |
| 6 | Bevacizumab ± thalidomide | VEGF-A | 4 | Bevacizumab ± thalidomide | SD = 37–350 days; PR = 33%; PD = 67% | ||||
| Badros et al. (2017) Phase II | 48 | Pembrolizumab | PD-1 | 3 (2–5) | 200 mg iv. ×2 wk | 28 | Pem + Pom + Dex | mPFS = 17.4 m; OR = 60%; VGPR = 19%; PR = 33% | [46] |
| Lesokhin et al. (2016) Phase Ib | 27 | Nivolumab | PD-1 | 3 (1–12) | 1–3 mg/kg ×2 wk | NR | MoAb monotherapy | mPFS = 10 wk; OR = 4%; SD = 63%; CR = 4% | [47] |
| Efebera et al. (2015) Phase I/II | 12 | Pidilizumab | PD-1 | 2 (2–11) | 1.5–6 mg/kg every 28 days | NR | Pidilizumab + Len (15–25 mg) | VGPR: n = 3; PR: n = 1 | [48] |
| Berdeja et al. (2012), Phase I | 44 (39 REP) | Lorvotuzumab mertansine | CD56 | 2 (1–11) | 75–112 mg/m2 | NR | LM + Len (20 mg) + Dex (40 mg) | ORR = 59%; sCR: n = 1; CR: n = 1; VGPR: n = 8; PR: n = 9 | [49] |
| Chanan et al. (2010) Phase I | 37 | Lorvotuzumab mertansine | CD56 | 6 | 40–140 mg/m2 ×1 wk | NR | Monotherapy | SD = 41% | [50] |
| Kelly et al. (2016) Phase I/IIa | 47 (43 REP) | Indatuximab ravtansine (ADC) | CD138 | 1–6 | 80–100 mg/m2 | NR | Indatuximab + Dex + Len | ORR = 78%; PR = 33/47; mPFS 16.4 m | [51] |
| 17 | >2 | NR | Indatuximab + Dex + pomalidomide | ORR = 79%; VGPR = 4; PR = 7 | |||||
| Kelly et al. (2014) Phase I/IIa | 45 (36 REP) | Indatuximab ravtansine (ADC) | CD138 | 3 | 80, 100, 120 mg/m2 | NR | Indatuximab + Len + Dex | ORR = 78%; sCR = 1; CR = 2; VGPR = 10; PR = 15; SD = 2 | [52] |
| Heffner et al. (2012) Phase I/IIa | 29 (23 REP) | Indatuximab ravtansine (ADC) | CD138 | 2 (1–11) | 40–160 mg/m2 | NR | Monotherapy | PR = 1; SD = 11; mPFS = 112 days (90–245) | [53] |
ADC: Antibody drug conjugate; BAFF: B-cell activating factor; Bor: Bortezomib; CR: Complete response; Dex: dexamethasone; Len: Lenalidomide; LM: Lorvotuzumab mertansine; m: month; MoAb: Monoclonal antibody; mPFS: Median progression free survival; MR: Minimal response; NE: Not evaluable; NR: Not reported; OR: overall response; ORR: Objective response rate; OS: Overall survival; PD: Progressive disease; Pem: Pembrolizumab; Pom: Pomalidomide; PR: Partial response; REP: Response evaluable patient; sCR: Stringent complete response; SD: Stable disease; Tab: Tabalumab; VEGF: Vascular endothelial growth factor; VGPR: Very good partial response; wk: Week.