Single-agent response in human and Vk*MYC MM
| Drug . | Group/target . | Clinical response* . | Vk*MYC response† . |
|---|---|---|---|
| Agents with clinical response rate > 20% | |||
| Melphalan | Alkylating agent | 36%1 | 78% |
| Cyclophosphamide | Alkylating agent | 33%1 | 100% |
| Dexamethasone | Glucocorticoid R | 27%36 | 50% |
| Bortezomib | Proteasome | 35%33 | 100% |
| Carfilzomib | Proteasome | 46%34 | 60% |
| Pomalidomide | Immunomodulator | 54%41 | 25% |
| Lenalidomide | Immunomodulator | 50%39 | 0% |
| Agents with clinical response rate < 20% | |||
| Pegylated liposomal doxorubicin (PLD) | Anthracycline antibiotic | No24 | 0% |
| Atorvastatin | HMG-CoA reductase | No32 | 0% |
| Lovastatin | HMG-CoA reductase | No32 | 0% |
| Cladribine | Purine analog | 0%35 | 0% |
| Fludarabine | Purine analog | 0%37 | 0% |
| Hydroxyurea | Ribonucleotide reductase | 0%38 | 0% |
| Vincristine | Tubulin | 10%5 | 0% |
| Panobinostat | HDAC | 3%29 | 67% |
| Romidepsin | HDAC | 0%42 | 33% |
| Vorinostat | HDAC | 0%17 ‡ | 40% |
| Perifosine | Membrane phospholipids | 0%40 | 38% |
| TACI-mFc4 | APRIL-TACI-BCMA | 0%30 | 43% |
| Agents with unknown clinical response rate | |||
| J1 | Alkylator pro-drug | n.a. | 66% |
| JQ1 | Bromodomain 4 | n.a. | 57% |
| TH-302 | Hypoxia-activated alkylator | n.a. | 44% |
| PR-047 | Proteasome | n.a. | 43% |
| Paclitaxel protein-bound | Microtubules | n.a. | 23% |
| Obatoclax mesylate | Pan BCL2 family antagonist | n.a. | 20% |
| SNS-032 | CDK-2-7-9 | n.a. | 9% |
| Ciclopirox olamine | Antimycotic | n.a. | 0% |
| Purvalanol A | CDK-1-2-5 | n.a. | 0% |
| AUY922-AG | HSP90 | n.a. | 0% |
| γ-secretase XII inhibitor | Notch | n.a. | 0% |
| CTLA4-Ig | B7 | n.a. | 0% |
| TAK-901 | Aurora kinase B | n.a. | 0% |
| BAFFR-mFc4 | BAFFR | n.a. | 0% |
| GDC-0941 | PI3K | n.a. | 0% |
| BEZ-235-AN | PI3K | n.a. | 0% |
| Decitabine | Cytidine analog | n.a. | 0% |
| Drug . | Group/target . | Clinical response* . | Vk*MYC response† . |
|---|---|---|---|
| Agents with clinical response rate > 20% | |||
| Melphalan | Alkylating agent | 36%1 | 78% |
| Cyclophosphamide | Alkylating agent | 33%1 | 100% |
| Dexamethasone | Glucocorticoid R | 27%36 | 50% |
| Bortezomib | Proteasome | 35%33 | 100% |
| Carfilzomib | Proteasome | 46%34 | 60% |
| Pomalidomide | Immunomodulator | 54%41 | 25% |
| Lenalidomide | Immunomodulator | 50%39 | 0% |
| Agents with clinical response rate < 20% | |||
| Pegylated liposomal doxorubicin (PLD) | Anthracycline antibiotic | No24 | 0% |
| Atorvastatin | HMG-CoA reductase | No32 | 0% |
| Lovastatin | HMG-CoA reductase | No32 | 0% |
| Cladribine | Purine analog | 0%35 | 0% |
| Fludarabine | Purine analog | 0%37 | 0% |
| Hydroxyurea | Ribonucleotide reductase | 0%38 | 0% |
| Vincristine | Tubulin | 10%5 | 0% |
| Panobinostat | HDAC | 3%29 | 67% |
| Romidepsin | HDAC | 0%42 | 33% |
| Vorinostat | HDAC | 0%17 ‡ | 40% |
| Perifosine | Membrane phospholipids | 0%40 | 38% |
| TACI-mFc4 | APRIL-TACI-BCMA | 0%30 | 43% |
| Agents with unknown clinical response rate | |||
| J1 | Alkylator pro-drug | n.a. | 66% |
| JQ1 | Bromodomain 4 | n.a. | 57% |
| TH-302 | Hypoxia-activated alkylator | n.a. | 44% |
| PR-047 | Proteasome | n.a. | 43% |
| Paclitaxel protein-bound | Microtubules | n.a. | 23% |
| Obatoclax mesylate | Pan BCL2 family antagonist | n.a. | 20% |
| SNS-032 | CDK-2-7-9 | n.a. | 9% |
| Ciclopirox olamine | Antimycotic | n.a. | 0% |
| Purvalanol A | CDK-1-2-5 | n.a. | 0% |
| AUY922-AG | HSP90 | n.a. | 0% |
| γ-secretase XII inhibitor | Notch | n.a. | 0% |
| CTLA4-Ig | B7 | n.a. | 0% |
| TAK-901 | Aurora kinase B | n.a. | 0% |
| BAFFR-mFc4 | BAFFR | n.a. | 0% |
| GDC-0941 | PI3K | n.a. | 0% |
| BEZ-235-AN | PI3K | n.a. | 0% |
| Decitabine | Cytidine analog | n.a. | 0% |
MM indicates multiple myeloma; HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA; n.a., not available; and HDAC, histone deacetylase.
Clinical response is the response rate (defined as greater than 50% reduction in tumor burden) for the drug as a single agent in MM. Note that for PLD there is no single agent response rate data, but the addition of PLD to dexamethasone did not increase the response rate over dexamethasone alone.
Vk*MYC response is the response rate (defined as > 50% reduction in the M-spike at 14 days) for the drug as a single agent in Vk*MYC MM.
In a randomized trial, vorinostat combined with bortezomib demonstrated a significantly increased response rate compared to bortezomib alone (56% vs 41%, P < .0001).21