Table 6.
Summary of the most relevant clinical trials with Hsp-90 inhibitors, agents interfering with signaling pathways, and agents with other mechanisms of action in MM
| Mechanism | Name | Combinations | Phase | n | Previous lines | ORR (≥ PR) | CBR (≥ MR) | Reference |
|---|---|---|---|---|---|---|---|---|
| Hsp-90 inhibitors | ||||||||
| Hsp-90 inhibitors | Tanespimycin | 1 | 29 | 4 (2–19) | 0% | 3% | Richardson BJH 2010200 | |
| + Bort-Dex | 1 | 22 | 5 (3–11) | 9% | 15% | Richardson BJH 2010145 | ||
| + Bort-Dex | 1/2 | 72 | 5 (1–15) | 15% | 27% | Richardson BJH 2011146 | ||
| Signaling pathways inhibitors | ||||||||
| AKT inhibitors | Perifosine | +/− Dex* | 2 | 64 | 4(1–11) | − Dex: 0% + Dex: 13% |
− Dex: 2% + Dex: 38% |
Richardson ASH 2007147 |
| + Bort +/− Dex** | 1/2 | 84 | 5 (1–13) | − Dex: 23% + Dex: 32% |
− Dex: 41% + Dex: 64% |
Richardson JCO 2011148 | ||
| + Len Dex | 1 | 32 | 2 (1–4) | 50% | 73% MR | Jakubobiak BJH 2012149 | ||
| GSK2110183 | 1 | 34 | 5 (2–8) | 9% | 19% | Spencer ASH 2011150 | ||
| mTORC1 inhibitors | Everolimus | 1/2 | 17 | - | 7% | 7% | Guenther ASCO 2010151 | |
| + Len | 1 | 26 | 4 | 21% | 58% | Mahindra ASH 2010154 & Yee ASH 2011155 | ||
| Temsirolimus | 2 | 16 | 2 (1–5) | 6% | 38% | Farag Leuk Research 2009152 | ||
| + Bort | 1/2 | 63 | 5 (1–14) | 28% | 42% | Ghobrial Lancet Oncol 2011153 | ||
| + Len | 1 | 21 | 3 (1–6) | 12% | 47% | Hofmeister JCO 2011156 | ||
| mTORC1/C2 inhibitors | MLN0128 INK128 | 1 | 30 | 2 (1–10) | 0% | 3% | Ghobrial ASH 2012157 | |
| Farnesyl transferase inhibitors | Tipifarnib | 2 | 43 | 4(1–6) | 0% | - | Alsina Blood 2004158 | |
| p38/MAPK inhibitors | SCIO-469 | +/− Bort*** | 2 | 62 | 5 | − Bort: 0% + Bort: 26% |
− Bort: 0% + Bort: 32% |
Siegel ASH 2006160 |
| p38/JNK activators | Plitidepsin (Aplidin) | +/− Dex** | 2 | 51 | 4 (1–8) | − Dex: 4% + Dex: 11% |
− Dex: 13% + Dex: 22% |
Mateos Clin Cancer Res 2010161 |
| MEK inhibitors | Selumetinib | 2 | 37 | 5 (2–11) | 8% | 8% | Holkova ASH 2011159 | |
| Other mechanisms | ||||||||
| TRAIL activators | Circularly permuted TR AIL (CPT) | 1b | 47 | - | 19% | 33% | Chen ASH 2012164 | |
| 2 | 27 | - | 33% | - | Chen ASH 2012165 | |||
| + Thal | 2 | 43 Thal- refractory | - | 22% | 34% | Chen ASH 2012166 | ||
| DNA damaging agents | Zalypsis | 1/2 | 22 | 3 (2–5) | 6% | 31% | Ocio ASH 2012167 | |
| PARP 1/2 inhibitors | Veliparib | + Bort | 1 | - | 3 (1–9) | 50% | 87% | Neri ASH 2012168 |
| Hypoxia-activated alkylator | TH-302 | + Dex | 1 | 11 | 6 (3–10) | 22% | 44% | Ghobrial ASCO 2013170 |
*
Dexamethasone added if PD
**
Dexamethasone added if < MR at cycle 4
***
Bortezomid added if < MR