What is the treatment for Mycosis Fungoides (Cutaneous T-cell Lymphoma)/Sézary Syndrome?

From the Guidelines

The treatment for mycosis fungoides and Sézary syndrome typically follows a stage-based approach, with skin-directed therapies being the mainstay for early-stage disease (IA-IIA) and systemic treatments necessary for advanced disease (IIB-IV) 1. For early-stage disease, skin-directed therapies include:

• Topical corticosteroids
• Topical retinoids (bexarotene gel)
• Topical chemotherapy (nitrogen mustard, carmustine)
• Phototherapy (PUVA or UVB)
• Localized radiation therapy In patients with early-stage MF (stage IA–IIA), a stage-adapted conservative therapeutic approach is recommended, with nb-UVB used in patients with patches or very thin plaques, and PUVA therapy preferred in patients with thicker plaques 1. For advanced disease, systemic treatments include:
• Oral retinoids (bexarotene)
• Interferon alfa
• Histone deacetylase inhibitors (vorinostat, romidepsin)
• Monoclonal antibodies (mogamulizumab)
• Chemotherapy (gemcitabine, liposomal doxorubicin) Extracorporeal photopheresis is particularly effective for Sézary syndrome, typically administered on two consecutive days every 2-4 weeks 1. Allogeneic stem cell transplantation may be considered for young, fit patients with advanced disease, particularly those with refractory, progressive MF or Sézary syndrome 1. Treatment selection depends on disease stage, patient characteristics, and treatment availability, with combination approaches often used for refractory disease 1. Regular skin examinations and blood monitoring are essential during treatment to assess response and manage side effects. In patients with advanced and refractory disease, gemcitabine or liposomal doxorubicin may be considered, but responses are generally short-lived 1. Local palliation of cutaneous and extracutaneous lesions may be achieved with local radiotherapy to doses of 8 Gy 1. The optimal conditioning regimen and timing for an allogeneic transplant are currently unknown, and further research is needed to determine the best approach for these patients 1.

From the FDA Drug Label

VALCHLOR is a prescription medicine used on the skin (topical) to treat people with Stage 1A and 1B mycosis fungoides-type cutaneous T-cell lymphoma who have received previous skin treatment. The treatment for mucosos fungoides/Sèsary síndrome (specifically mycosis fungoides-type cutaneous T-cell lymphoma) is topical mechlorethamine (VALCHLOR), for patients who have received prior skin-directed therapy, specifically for Stage IA and IB. 2

• Key points:
  • Mechlorethamine is an alkylating agent that inhibits rapidly proliferating cells.
  • VALCHLOR is applied topically on a daily basis.
  • Patients should be evaluated for a response on a monthly basis for the first 6 months and then every 2 months for the last 6 months.
  • A response is defined as greater than or equal to 50% reduction in baseline CAILS score or SWAT score. 2 Note: Sèsary síndrome is not explicitly mentioned in the provided drug labels, but it is a more aggressive form of cutaneous T-cell lymphoma, and the treatment may be different. 2

From the Research

Treatment Overview

• The treatment of mycosis fungoides (MF) and Sézary syndrome (SS) should follow a stage-based approach, aiming to minimize toxicity while achieving optimal benefits 3, 4.
• For early-stage MF (IA-IIA), skin-directed therapy (SDT) is the primary treatment, including:
  • Topical corticosteroids
  • Phototherapy
  • Topical chemotherapy
  • Topical retinoids
  • Radiotherapy 3, 4, 5

Systemic Therapy

• For aggressive or recalcitrant early-stage MF, or advanced-stage MF, systemic therapy should be considered, including:
  • Interferon-alpha
  • Oral retinoids (e.g., bexarotene, acitretin)
  • Histone deacetylase inhibitors (HDACi)
  • Fusion toxin denileukin diftitox
  • Chemotherapy drugs 3, 4, 6
• Combined drug regimens can be used to achieve a synergistic effect while lowering individual drug doses 3
• Chemotherapy should be reserved for cases where other systemic drugs have failed or are contraindicated, except in aggressive stages 3

Novel Therapies

• Novel drugs, such as brentuximab vedotin and mogamulizumab, have shown promise in treating MF and SS, particularly in cases with CD30-positive malignant cells or blood involvement 6
• Investigational oral therapies, including tenalisib, duvelisib, and lenalidomide, are being explored for the treatment of MF and SS 5

Treatment Considerations

• Treatment should be tailored to the individual patient, taking into account symptom severity, patient age, and comorbidities 7, 6
• Allogeneic hematopoietic stem cell transplantation may be considered for advanced-stage patients with a short life expectancy, as it offers a chance of cure with durable complete remission 6