Selected novel drugs being evaluated in current clinical trials for MF/SS
| Drug class . | Examples . | Comments . |
|---|---|---|
| HDACi | Romidepsin81 Panobinostat110 Belinostat83 | Vorinostat is approved for relapsed, refractory CTCL, which has led to investigation to other HDACi in CTCL and PTCL; a number are undergoing regulatory approval process; response rates and toxicities are similar |
| Monoclonal antibodies | Zanolimumab89 | ORR of 50%+ as single agent in early studies but of relatively short duration; well tolerated with little infection risk; combination studies planned |
| Alemtuzumab84-86,88 | Single-agent studies with ORR of 40%+ but short duration; immunosuppressive; combination studies underway | |
| Purine nucleoside phosphorylase inhibitor | Forodesine (BCX-1777)111 | Single-agent activity of 30%+ with durable remissions observed; well tolerated and convenient (oral) |
| Proteasome inhibitors | Bortezomib112 | Single-agent activity observed in heavily pretreated patients; generally well tolerated with minimal myelosuppression; combination studies planned |
| IMiDs | Lenalidomide113 | Single-agent activity observed in heavily pretreated patients; generally well tolerated, but fatigue appears dose-limiting; maintenance studies being considered |
| Synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG-ODN) | PF-3512676 | CpG-ODN have potent immunostimulatory effects and activate professional antigen-presenting cells that express the target receptor, Toll-like receptor 9114 |
| Retinoids | Tazarotene115 | Novel synthetic retinoid |
| Fusion toxins | Anti-Tac(Fv)-PE38 (LMB-2)116 | Fusion toxins, which combines a target cell binding domain linked to a bacterial toxin |
| Antifolate | Pralatrexate117 | Pralatrexate is a novel antifolate designed to have high affinity for the reduced folate carrier type 1 |
| Drug class . | Examples . | Comments . |
|---|---|---|
| HDACi | Romidepsin81 Panobinostat110 Belinostat83 | Vorinostat is approved for relapsed, refractory CTCL, which has led to investigation to other HDACi in CTCL and PTCL; a number are undergoing regulatory approval process; response rates and toxicities are similar |
| Monoclonal antibodies | Zanolimumab89 | ORR of 50%+ as single agent in early studies but of relatively short duration; well tolerated with little infection risk; combination studies planned |
| Alemtuzumab84-86,88 | Single-agent studies with ORR of 40%+ but short duration; immunosuppressive; combination studies underway | |
| Purine nucleoside phosphorylase inhibitor | Forodesine (BCX-1777)111 | Single-agent activity of 30%+ with durable remissions observed; well tolerated and convenient (oral) |
| Proteasome inhibitors | Bortezomib112 | Single-agent activity observed in heavily pretreated patients; generally well tolerated with minimal myelosuppression; combination studies planned |
| IMiDs | Lenalidomide113 | Single-agent activity observed in heavily pretreated patients; generally well tolerated, but fatigue appears dose-limiting; maintenance studies being considered |
| Synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG-ODN) | PF-3512676 | CpG-ODN have potent immunostimulatory effects and activate professional antigen-presenting cells that express the target receptor, Toll-like receptor 9114 |
| Retinoids | Tazarotene115 | Novel synthetic retinoid |
| Fusion toxins | Anti-Tac(Fv)-PE38 (LMB-2)116 | Fusion toxins, which combines a target cell binding domain linked to a bacterial toxin |
| Antifolate | Pralatrexate117 | Pralatrexate is a novel antifolate designed to have high affinity for the reduced folate carrier type 1 |
IMiDs indicates immunomodulatory drugs; and CpG-ODN, cytosine-phosphate-guanosine oligodeoxynucleotide.