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 |