From the Guidelines
Sézary syndrome should be treated with a multidisciplinary approach, prioritizing systemic therapies such as extracorporeal photopheresis (ECP), interferon, retinoids, and chemotherapy agents, with allogeneic stem cell transplantation considered for eligible patients, as recommended by the most recent guidelines 1.
Key Considerations
- Sézary syndrome is a rare and aggressive type of cutaneous T-cell lymphoma characterized by the presence of malignant T-cells in the skin, lymph nodes, and blood.
- Patients typically present with generalized erythroderma, intense pruritus, lymphadenopathy, and circulating atypical T-cells called Sézary cells.
- Systemic treatment is required, with ECP, either alone or in combination with other treatment modalities, suggested as the treatment of choice in Sézary syndrome and erythrodermic mycosis fungoides 1.
Treatment Options
- ECP has been shown to have overall response rates ranging from 30% to 80%, with complete response rates ranging from 14% to 25% 1.
- Other treatment options include interferon, retinoids, histone deacetylase inhibitors, and chemotherapy agents.
- Allogeneic stem cell transplantation may be considered for eligible patients, particularly those with refractory, progressive disease 1.
Supportive Care
- Supportive care is essential, including antihistamines for itching, moisturizers for skin dryness, and antibiotics for secondary infections.
- Skin-directed therapies such as topical corticosteroids, phototherapy, and radiation therapy can help manage skin symptoms.
Prognosis
- Prognosis is generally poor, with a median survival of 2-4 years, though early diagnosis and aggressive treatment can improve outcomes.
From the FDA Drug Label
Objective disease response was evaluated according to a composite endpoint that included assessments of skin involvement, lymph node and visceral involvement, and abnormal circulating T-cells (“Sézary cells”)
The drug labels provide information on the treatment of CTCL, which includes Sézary syndrome, with romidepsin. Sézary cells are mentioned as part of the composite endpoint for evaluating objective disease response.
- The primary efficacy endpoint was overall objective disease response rate (ORR) based on the investigator assessments.
- The studies included patients with CTCL, including those with Sézary syndrome, who received romidepsin at a starting dose of 14 mg/m2 infused over 4 hours on days 1,8, and 15 every 28 days.
- The response rates for CTCL patients are provided in Table 4, with an overall response rate (ORR) of 34% in Study 1 and 35% in Study 2 2.
From the Research
Definition and Characteristics of Sezary Syndrome
- Sezary syndrome (SS) is a rare and aggressive type of cutaneous T cell lymphoma (CTCL) characterized by an intensely pruritic, exfoliative rash, known as erythroderma, with cutaneous and systemic dissemination of clonal CD4+ T cells into the blood and lymph nodes 3.
- It is the leukemic form of primary cutaneous T-cell lymphoma, with the lowest reported median survival of all cutaneous lymphomas 4.
Clinical Aspects and Prognostic Factors
- The median overall survival (OS) rate of SS patients is 2-4 years 5.
- Univariate analyses identified older age (>65 years) and male sex as poor prognostic factors 5.
- Hypereosinophilia, highly elevated β2µglobulin >3500 µg/L, male sex, and highly elevated LDH>450 U/L resulted in statistical power as prognostic variables 6.
- Targeted therapies were effective in treating refractory/relapsed SS patients with a durable response 5.
Treatment Options
- Novel systemic therapies are generally prescribed to patients with advanced-stage disease or those with early-stage disease refractory to skin-directed therapies 7.
- Biological agents such as interferon alfa, bexarotene, histone deacetylase inhibitors (vorinostat, romidepsin), brentuximab vedotin, and mogamulizumab are used to treat SS 7.
- Extracorporeal photopheresis is particularly effective for patients with Sézary Syndrome 7.
- Allogeneic transplantation is becoming increasingly used for younger patients 7.
- A three-line treatment approach, including extracorporeal photopheresis plus immunomodulator/s plus photo-photochemotherapy, was the most used first-line option for induction of remission 6.