What are the treatment options for Mycosis fungoides?

Treatment Options for Mycosis Fungoides

Skin-directed therapy is the most appropriate first-line treatment for early stages of mycosis fungoides (stages IA-IIA), with the choice depending on the extent of cutaneous disease and plaque thickness. 1

Treatment by Stage

Early Stage Disease (IA-IIA)

First-line options:

• Limited patches/thin plaques (Stage IA):

  • Topical corticosteroids
  • Narrow-band UVB phototherapy (preferred for patches and thin plaques) 1, 2
  • Topical mechlorethamine (nitrogen mustard) 0.016% gel - FDA approved for stage IA and IB 3
  • Local radiotherapy for isolated lesions 1

• Extensive patches/plaques (Stage IB):

  • PUVA (psoralen + UVA) phototherapy (preferred for thicker plaques) 1, 2
  • Narrow-band UVB (for thinner lesions) 4
  • Topical mechlorethamine 3
  • Total skin electron beam therapy (TSEB) 1

Second-line options for resistant early-stage disease:

• Combined PUVA and α-interferon 1
• Combined PUVA and retinoids (including bexarotene) 1
• Bexarotene gel (topical) 1
• Low-dose methotrexate 5

Advanced Disease (IIB-IV)

Stage IIB (tumors):

• Combination of skin-directed and systemic therapy 1
• Local radiotherapy for tumors 1
• PUVA combined with interferon or retinoids 1
• Total skin electron beam therapy (TSEB) with additional therapy for significant hematological involvement 1

Stage III (erythroderma) and IV (nodal/visceral):

• Extracorporeal photopheresis (ECP) - particularly effective for erythrodermic disease with 35-71% response rates 1

• Immunotherapy approaches 1

• Systemic retinoids (bexarotene) 1, 5

• HDAC inhibitors (vorinostat) 1, 5

• Gemcitabine or liposomal doxorubicin 1

• Denileukin diftitox 1

• Multi-agent chemotherapy: Only indicated for patients with:

  • Effaced lymph nodes
  • Visceral involvement (stage IV)
  • Widespread tumor stage MF uncontrolled with skin-targeted and immunomodulating therapies 1

Special Considerations

Phototherapy Protocols

• For inducing remission: Three treatment sessions per week of PUVA or NB-UVB until complete remission 2
• Maintenance therapy is not routinely recommended but may be used for patients with early relapse 2
• NB-UVB shows comparable effectiveness to PUVA with fewer side effects and less carcinogenicity 4
• Complete remission rates: 81% for NB-UVB vs 71% for PUVA in early-stage disease 4

CD30+ Variants

• Primary cutaneous CD30+ lymphoproliferative disorders have excellent prognosis (96-100% 5-year survival) 1
• Lymphomatoid papulosis: Low-dose methotrexate or PUVA therapy 1
• Primary cutaneous anaplastic large cell lymphoma: Skin-directed therapy unless extensive cutaneous or systemic involvement 1

Treatment Pitfalls to Avoid

1. Avoid aggressive chemotherapy in early disease - Early aggressive chemotherapy has significant side effects without improving survival 1
2. Recognize sanctuary sites - Flexural areas often fail to respond completely to phototherapy 1
3. Monitor for side effects:
   • PUVA: Increased skin cancer risk with cumulative doses 2
   • Mechlorethamine: Risk of contact dermatitis, secondary skin cancers 3
   • Systemic therapies: Monitor for specific toxicities (hyperlipidemia with bexarotene, etc.) 1
4. Consider quality of life - In treatment-resistant late-stage disease, prioritize patient's quality of life when selecting therapies 1

Prognosis

• Stage IA: Normal life expectancy in most cases 1
• Stage IB/IIA: 73-86% and 49-73% 5-year survival, respectively 1
• Stage IIB: 40-65% 5-year survival 1
• Stage III: 45-57% 5-year survival 1
• Stage IVA: 15-40% 5-year survival 1
• Stage IVB: 0-15% 5-year survival 1
• Sézary syndrome: Median survival of 32 months from diagnosis 1

The treatment approach should be stage-adapted, with skin-directed therapies for early disease and systemic approaches reserved for advanced or refractory cases. Radiation therapy remains highly effective at all stages due to the radiosensitivity of this lymphoma 1, 6.