Version May 2024
| Agent | Comment | Combination therapy | US FDA status |
| Primary treatment (Group "A" therapies) | |||
| Extracorporeal photopheresis (ECP) | Only available at specialized centers; does not cause generalized immunosuppression | Can be combined with other systemic (retinoid, low dose methotrexate, HDAC inhibitor, interferon) or skin-directed (topicals, phototherapy, TSEBT) therapy | Approved |
| Retinoids (bexarotene, acitretin, isotretinoin, all-trans retinoic acid) | Teratogenic; common side effects include hyperlipidemia and central hypothyroidism (bexarotene) | Can be combined with other systemic (ECP, interferon) or skin directed (PUVA, TSEBT) therapy | Bexarotene approved for refractory disease |
| Interferons (interferon alfa, interferon gamma) | Use with caution in patients with concomitant autoimmune conditions (ie, rheumatoid arthritis) or solid organ transplant patients | Can be combined with other systemic (ECP, bexarotene) or skin directed (topicals, PUVA, TSEBT) therapy | Off label (interferon alfa is US FDA approved for non-Hodgkin lymphoma, which includes mycosis fungoides/Sézary syndrome) |
| Histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin) | Fatigue, nausea, diarrhea, thrombocytopenia, nonspecific electrocardiogram effects | Can be combined with other systemic (ECP, interferon) or skin-directed (TSEBT) therapy | Romidepsin approved for the treatment of progressive, persistent, or recurrent disease on or following at least one prior systemic therapy; vorinostat approved following two systemic therapies |
| Low-dose methotrexate | Teratogenic; mild generalized immunosuppression; liver toxicity | Can be combined with other systemic (ECP, interferon, HDAC inhibitor) or skin directed therapy | Approved |
| Brentuximab vedotin | Peripheral neuropathy | US FDA approved for CD30+ disease after at least one prior therapy | |
| Mogamulizumab | Infusion reactions, skin eruptions, diarrhea, nausea, thrombocytopenia, dysgeusia, renal toxicity | US FDA approved for relapsed or refractory disease after at least one prior systemic therapy | |
| Secondary treatment (Group "B" therapies): to be used after inadequate response, refractory disease, or progression despite primary treatments | |||
| Pegylated liposomal doxorubicin | Myelosuppressive | Off label | |
| Gemcitabine | Myelosuppressive | Off label | |
| Alemtuzumab | Not commercially available | Off label | |
| Chlorambucil | Myelosuppressive | Off label | |
| Fludarabine | Myelosuppressive | Can be combined with cyclophosphamide | Off label |
| Cladribine | Myelosuppressive | Off label | |
| Pentostatin | Myelosuppressive | Off label | |
| Intermediate dose methotrexate | Myelosuppressive | Approved | |
| Pralatrexate (low dose) | Stomatitis, skin toxicity | Approved for refractory disease | |
| Pembrolizumab | Off label | ||
| Allogeneic hematopoietic cell transplantation | |||
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