Targeted novel therapies in relapsed/refractory peripheral T-cell lymphomas (PTCLs).
| Agents . | Target . | PTCL (n) . | Clinical studies (ref) . |
|---|---|---|---|
| Abbreviations: ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; ATLL, adult T-cell lymphoma/leukemia; CMV, cytomegalovirus; IL, interleukin; MTD, maximum tolerated dose; ORR, overall response rate; PTCL, peripheral T-cell lymphoma; TRM, treatment-related mortality; ATLL, adult T-cell lymphoma/leukemia (HTLV1) | |||
| Nucleoside analogs | |||
| Gemcitabine | Nucleoside analog; non-specific DNA synthesis inhibition | PTCL (10) | 60% ORR48 |
| AraG | |||
| 506U78 (Nelarabine)-pro-drug | Nucleoside analog; selective toxicity for T cells | PTCL (8) | Phase II ORR 14%49 Toxicity: 2 early deaths |
| Immunotoxin | |||
| Denileukin difitox | IL-2 receptor | PTCL (14) | Phase II ORR 50%50 |
| Histone deaceylase Inhibitors | |||
| Depsipeptide | Histone de-acetylation | PTCL (19) | Phase II ORR 26%52 |
| Immunotherapy | |||
| Anti-CD25, yttrium-90 labeled | CD25 | ATLL (18) | Phase I/II ORR 56%51 |
| Alemtuzumab | CD52 | PTCL (14) | Pilot ORR 36%53 Toxicity: CMV reactivation 43%; 36% TRM—study closed early |
| Alemtuzumab + fludarabine, cyclophosphamide + doxorubicin | CD52 | PTCL except ALK+ ALCL (23) included untreated patients | Pilot ORR 61%54 Toxicity: 81% grade III/IV leukopenia; 56% CMV reactivation |
| SGN30 (chimeric monoclonal antibody) | CD30 | ALCL (5) | SGN30 phase II OR 33%55 Toxicity: well tolerated |
| MDX-060 (fully human anti-CD30) | CD30 | ALCL (6) | MDX-060 ORR 33% Toxicity: no MTD56 |
| 5F11 (fully human anti-CD30) | CD30 | CD30+ ALCL | 5F11 phase I study ongoing in CD30+ lymphomas |
| KM2760—Anti-CCR4 (chimeric monoclonal antibody) | CCR4 | ATLL CCR4+ PTCLs | Preclinical studies ongoing57 |
| Agents . | Target . | PTCL (n) . | Clinical studies (ref) . |
|---|---|---|---|
| Abbreviations: ALCL, anaplastic large cell lymphoma; ALK, anaplastic lymphoma kinase; ATLL, adult T-cell lymphoma/leukemia; CMV, cytomegalovirus; IL, interleukin; MTD, maximum tolerated dose; ORR, overall response rate; PTCL, peripheral T-cell lymphoma; TRM, treatment-related mortality; ATLL, adult T-cell lymphoma/leukemia (HTLV1) | |||
| Nucleoside analogs | |||
| Gemcitabine | Nucleoside analog; non-specific DNA synthesis inhibition | PTCL (10) | 60% ORR48 |
| AraG | |||
| 506U78 (Nelarabine)-pro-drug | Nucleoside analog; selective toxicity for T cells | PTCL (8) | Phase II ORR 14%49 Toxicity: 2 early deaths |
| Immunotoxin | |||
| Denileukin difitox | IL-2 receptor | PTCL (14) | Phase II ORR 50%50 |
| Histone deaceylase Inhibitors | |||
| Depsipeptide | Histone de-acetylation | PTCL (19) | Phase II ORR 26%52 |
| Immunotherapy | |||
| Anti-CD25, yttrium-90 labeled | CD25 | ATLL (18) | Phase I/II ORR 56%51 |
| Alemtuzumab | CD52 | PTCL (14) | Pilot ORR 36%53 Toxicity: CMV reactivation 43%; 36% TRM—study closed early |
| Alemtuzumab + fludarabine, cyclophosphamide + doxorubicin | CD52 | PTCL except ALK+ ALCL (23) included untreated patients | Pilot ORR 61%54 Toxicity: 81% grade III/IV leukopenia; 56% CMV reactivation |
| SGN30 (chimeric monoclonal antibody) | CD30 | ALCL (5) | SGN30 phase II OR 33%55 Toxicity: well tolerated |
| MDX-060 (fully human anti-CD30) | CD30 | ALCL (6) | MDX-060 ORR 33% Toxicity: no MTD56 |
| 5F11 (fully human anti-CD30) | CD30 | CD30+ ALCL | 5F11 phase I study ongoing in CD30+ lymphomas |
| KM2760—Anti-CCR4 (chimeric monoclonal antibody) | CCR4 | ATLL CCR4+ PTCLs | Preclinical studies ongoing57 |