Table 2.
Non-surface receptor Antibodies targeting in Relapsed Refractory Multiple Myeloma.
| Author, Year, Study Design | No of Patients | Antibody | Target | Median Prior Therapies | Dose | No. of Cycles | Regimen | Outcome |
|---|---|---|---|---|---|---|---|---|
| Callander, 2009, NEJM. | 31/27(REP) | Bevacizumab (IgG1-kappa) | VEGF | 3 (1–7) | Bevacizumab 10 mg/kg × 2 weeks | 4 | Bevacizumab + Len (25mg) + Dex (40mg) | OR = 70%, CR = 15%, PR = 56%, PD = 11% |
| Somlo, 2011, Phase II, British Journal of Haematology. | 6 | Bevacizumab (IgG1-kappa) | VEGF-A | 3 (0–5) | Bevacizumab 10 mg/kg | 4 | Bevacizumab Monotherapy | PD = 29–69 days, SD = 238 days, SD = 16.6%, PD = 83% |
| 6 | Bevacizumab (IgG1-kappa) ± Thalidomide | VEGF-A | 4 | Bevacizumab ± Thalidomide | SD = 37–350 days, PR = 33%, PD = 67% | |||
| White, 2013, Phase II, Cancer. | 49 | Bevacizumab (IgG1-kappa) | VEGF | (1–3) | Bevacizumab 15 mg/kg I.V | 8 | Bevacizumab + Bor | ORR = 51%, PR = 16.3%, mPFS = 6.2 m |
| 53 | Placebo | Bor 1.3 mg/m2 | Placebo + Bor | ORR = 43.4%, PR = 7.5%, mPFS = 5.1 m | ||||
| Brighton, 2017, Phase II, ASH. | 74 | Siltuximab (IgG1) | IL-6 | NR | 15 mg/kg Q4 week vs. Placebo | NR | Siltuximab vs. placebo | 1-yr PFS 84.5% with siltuximab vs. 74.4% with placebo. |
| Orlowski, 2015, Phase II, American Journal of Hematology. | 142 | Siltuximab (IgG1) | IL-6 | 1–3 | Siltuximab 6 mg/kg | 4 | Siltuximab + Bor | mPFS = 8m, ORR = 55%, CR = 11%, OS = 30.8 m |
| 139 | Placebo | Placebo | Placebo + Bor | mPFS = 7.6, ORR = 47%, CR = 7%, OS = 36.8 m | ||||
| Voorhesse, 2009, Phase II, British Journal of Haematology. | 14 | Siltuximab (IgG1) | IL-6 | 4 | 6 mg/kg | 4 | Siltuximab monotherapy | No Response (CR/PR), SD = 62%, PD = 39% |
| 39 | Siltuximab (IgG1) | 6 mg/kg + 40g | Siltuximab + Dex | ORR = 23%, PR = 17%, MR = 6%, SD = 57%, PD = 17%, PFS = 3.7 m |
||||
| Suzuki, 2015, Phase I, International Journal of Hematology. | 9 | Siltuximab (IgG1) | IL-6 | 1–2 | 5.5/11 mg/kg | ≥ 9 | Siltuximab + Bor (1.3 mg/m2) + Dex (20 mg) | CR = 22%, PR = 44% |
| Rossi,2009, Phase I, British Journal of Cancer. | 12/11(REP) | Atacicept (IgG) | BAFF | NR | 2–10 mg/kg | 5 | Atacicept monotherapy | No ORR, PD = 54%, SD = 45% |
| Lida, 2016, Phase I, Cancer Science. | 4 | Tabalumab (IgG4) | BAFF | At least 1 | 100 mg + 1.3 mg/m2 + 20 mg | 3(2–11) | Tabalumab + Bor+ Dexa | ORR:100%, VGPR: 50% (n = 2), PR: 50% (n = 2) |
| 12 | Tabalumab (IgG4) | BAFF | At least 1 | 200 mg + 1.3 mg/m2 + 20 mg | 4.5 (1–15) | Tabalumab + Bor + Dexa | ORR: 41.7%, VGPR: 8.3% (n = 1), PR:33.3 %(n = 4), SD:16,7 %(n = 2), PD:25%(n = 3) |
|
| Reje, 2017, Phase II, British Journal of Haematology. | 74 | Tabalumab (IgG4) | BAFF | 1–3 | 100 mg | 8 or 10 | Tab + Bor + Dex | ORR = 58.1% |
| 74 | Tabalumab (IgG4) | BAFF | 300 mg | Tab + Bor + Dex | ORR = 59.5% | |||
| 72 | Placebo | no mAb | Placebo + Bor + Dex | ORR = 61.6% | ||||
| Lesokhin, 2016, Phase Ib, JCO. | 27 | Nivolumab (IgG4) | PD-1 | 3 (1–12) | 1–3 mg/kg x 2wk | NR | Nivolumab monotherapy | mPFS = 10 wk=K8, OR = 4%, SD = 63%, CR = 4% |
| Ansell, 2016, Phase I, ASH. | 7 | Nivolumab (IgG4) + Ipilimumab (IgG1) | PD-1 + CTLA-4 | 5 (range 2–20) | 3 mg/kg IV and 1 mg/kg IV every 3 weeks × 4 followed by Nivo 3 mg/kg every 2 week for up to 2 years. | NR | Nivolumab + Ipilimumab | mPFS = 2.2, mOS = 7.6, No ORR. SD 1 (14%) |
| Badros, 2017, Phase II, Blood. | 48 | Pembrolizumab (IgG4) | PD-1 | 3 (2–5) | 200 mg IV × 2 wk | 28 | Pembrolizumab + pom + Dex | 27 of 48 pts (56%) ORR > PR; sCR (n = 4, 8%), nCR (n = 3, 6%), VGFR (n = 6, 13%), PR (n = 14, 29%). |
| Ribrag, 2017, Phase Ib, Haematologica. | 30 | Pembrolizumab (IgG4) | PD-L1 | 4(2–12) | 100–200 mg/kg Qweek or Q 2week. | 6 (2–15) | Pembrolizumab monotherapy | SD: 57%. PD: 43%. |
| Efebera, 2015, Phase I/II, Blood. | 12 | Pidilizumab (IgG4) | PD-1 | 2 (2–11) | 1.5–6 mg/kg every 28 days | NR | Pidilizumab + Len (15–25mg) | VGPR n = 3, PR n = 1 |
| Fouquet, 2018, Phase I, Oncotarget. | 10/6 (REP) | F50067 (IgG1) | CXCR4 | NR | Dose-Group (mg/kg)s were analyzed for MDD 0.03, 0.1, 0.3, 1.0 | 21 | F50067 Monotherapy | ORR 66.7% (>PR). Objective response 66.7% (>SD) |
| 4/3 (REP) | F50067 (IgG1) | CXCR4 | NR | 0.03, 0.1. weekly or Q2 week | 15 | F50067 + Len-LoDex | Objective response 33.3% (>SD) ORR not available |
|
| Belch, 2011, Phase II, Haematologica. | Arm A = 35 | No mAb, only Bor | TRAILR1 | 1.6 | Velcade Dose: 1.3 mg/m2 on days 1, 4, 8, 11 Q21 D | Maximum 17 cycles (1year) | Bor | ORR 51.4% Median DOR 8.5 m. PR 18. Mean PFS 8.7 CI(7.6, 10.0) |
| Arm B10 = 33 | Mapatumumab (IgG1) | TRAILR1 | 1.6 | 10 mg/kg on d1 Q21 days | Maximum of 17 cycles (1year) | Bor + Mapatumumab | ORR 30.3%, Median DOR 9.3 m. PR 10. Mean PFS 4.7 CI(2.5, 7.4) p = 0.29 |
|
| Arm B20 = 36 | Mapatumumab (IgG1) | TRAILR1 | 1.6 | 20 mg/kg on Day 1 Q21 days | Maximum of 17 cycles (1year) | Bor + Mapatumumab | ORR 52.8%, Median DOR 7.6 m. PR 17 Mean PFS 5.7 CI(5.2, 8.9) p = 0.21 |
|
| Channan, 2010, Phase I, Blood. | 37 | Lorvotuzumab mertansine (ADC) (IgG1) | CD56 | 6 | 40–140 mg/m2 × wk | NR | Lorvotuzumab mertansine Monotherapy | SD = 41% |
| Berdeja. 2012, Phase I, JCO. | 44 (39REP) | Lorvotuzumab mertansine (IgG1) | CD56 | 2 (1–11) | 75–112 mg/m2 | NR | LM + LEN (20mg) + Dex (40mg) | ORR = 59%, sCR n = 1, CR n = 1, VGPR n = 8, PR n = 9 |
| Heffner, 2012, Phase I/IIa, Blood. | 29/23 (REP) | Indatuximab Ravtansine (ADC) (IgG1) | CD138 | 2 (1–11) | 40–160 mg/m2 | NR | Indatuximab Monotherapy | PR = 1, SD = 11, mPFS = 112 days (90–245) |
| Kelly K. R., 2014, PhaseI/IIa, Blood. | 45/36 (REP) | Indatuximab Ravtansine (ADC) (IgG1) | CD138 | 3 | 80, 100, 120 mg/m2 | NR | Indatuximab + dex + Len | ORR = 78%, sCR = 1, CR = 2, VGPR = 10, PR = 15, SD = 2 |
| Kelly K. R., 2016, PhaseI/IIa, Blood. | 47/43 (REP) | Indatuximab Ravtansine (ADC) (IgG1) | CD138 | 1–6 | 80–100 mg/m2 | NR | Indatuximab + dex + Len | ORR = 78%, PR = 33/47, mPFS 16.4m |
| 17 | > 2 | NR | Indatuximab + dex + Pomalidomide | ORR = 79%, VGPR = 4, PR = 7 |
Abbreviations: REP; Response evaluable patients, mAb; Monoclonal Antibodies, ADC; Antibody Drug Conjugate, BAFF; B cell activating factor, len; Lenalidomide, Dex; dexamethasone, Bor, Bortezomib, Tab; Tabalumab, pom; Pomalidomide, pem; pembrolizumab, m; months, ORR; Objective response rate, CR; Complete response, PR: partial response, VGPR; Very good partial response, MR; Minimal response, PD; Progressive disease, NE; Not evaluable, mPFS; median Progression free survival, sCR; stringent complete response, SD; Stable disease, NR; Not reported, wk; weeks, LM; Lorvotuzumab mertansine, NEJM; New England Journal of Medicine, ASH; American Society of Hematology, JCO; Journal of Clinical Oncology.