A long-term retrospective study by Zhuo-Fan Xu, MD, of the Chinese Academy of Medical Science in Beijing, and colleagues has revealed new factors that predict prognosis and can help in treatment selection for patients with advanced mycosis fungoides (MF) and Sezary syndrome (SS). The results, published in Hematology, confirm that patients with MF/SS experience a wide range of survival and risk of progression. The authors thus recommend that rheumatologists adopt disease-specific risk-stratification methods such as tumor-node-metastasis-blood (TNMB) staging, Modified Severity-Weighted Assessment Tool (mSWAT) scoring, and other prognostic indexes.
MF/SS comprise more than half of all cutaneous T-cell lymphoma diagnoses. MF, an indolent form of cutaneous T-cell lymphoma, evolves slowly through patch, plaque, and tumor stages. Most patients with early-stage MF have an excellent prognosis; however, in the later stages of the disease, MF develops into SS, a quickly progressive leukemic form of cutaneous T-cell lymphoma associated with erythroderma. The latest National Comprehensive Cancer Network guidelines for advanced-stage MF/SS recommend systemic therapy in combination with skin-directed therapy. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and histone deacetylase (HDAC) inhibitors. Unfortunately, very little data exist on the efficacy of the different therapeutic approaches. Moreover, while rheumatologists currently stratify risk and make treatment selections based on TNMB staging, few studies have investigated the prognostic value of clinical exams.
In the current study, the researchers sought to define the clinical characteristics of MF/SS in the Chinese population, evaluate existing and new prognostic factors, and compare outcomes among patients with MF/SS who are treated with different therapies. The study included 92 patients treated at Peking Union Medical College Hospital from 2013 to 2023 with immunomodulatory drugs, conventional chemotherapy, and targeting agents such as HDAC inhibitors, brentuximab vedotin, and PD1 inhibitors (pembrolizumab). All patients with early-stage disease received first-line treatment: skin-directed therapies or immunomodulatory therapy. The median follow-up time for the study was 38 months (range = 22-150 months). Thirteen of the patients had SS: nine with stage IVA and four with stage IVB. The authors emphasized in their paper that the long-term retrospective nature of the study means that, over time, there were changes in diagnostic methods and approaches in disease management that may have influenced the consistency of the cohort.
The researchers found that the five-year overall survival (OS) was 97.1% for patients with stage I disease, 85.8% for stage II, 57.3% for stage III, and 46.0% for stage IV. At advanced-stage disease, immunomodulatory therapies were associated with a higher response rate (70%) and longer survival (median OS not reached) than chemotherapy (38.6% response rate; 39.5 months OS) and HDAC inhibitor (33.3% response rate; 30 months OS). Patients in the immunomodulatory therapy group received interferon (single agent, n=20; double agent, n=9), acitretin (n=7), oral methotrexate (n=5), and cortisol (single agent, n=1; combination, n=3). Most patients received HDAC inhibitors (n=14) or gemcitabine (n=12) as second-line treatments.
A Cox regression analysis identified age of 50 years or older; white blood cell count (WBC) greater than or equal to 8 x 109/L; serum lactate dehydrogenase (LDH) greater than or equal to 250 U/L; β2-microglobulin greater than or equal to 4.50 mg/L; and stage IV disease were all associated with reduced OS. Age of 50 years or older, serum LDH greater than or equal to 250 U/L, and stage IV disease were associated with reduced progression-free survival (PFS). When the investigators performed a Kaplan-Meier analysis, they found that immunomodulatory therapy was associated with longer PFS.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Xu ZF, Chen H, Liu Y, et al. A retrospective study of prognostic factors and treatment outcome in advanced-stage mycosis fungoides and Sezary syndrome. Hematology. 2024;29(1):2366631.
