Prognostic Factors, Staging and Treatments in Advanced Stage Mycosis Fungoides and Sézary Syndrome

Introduction:

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas characterized by skin infiltration of neoplastic T lymphocytes. Mycosis fungoides (MF), and its leukemic variant Sézary syndrome (SS), are characterized by clonal proliferation of CD4+/CD45R0+ effector or central memory CD4+ T cells, respectively, with partial loss of mature T-cell antigens.

Objectives: To evaluate prognostic factors including risk of disease progression from initial presentation and treatment in a prospectively collected, single center cohort of 168 advanced MF/SS patients 168 patients evaluated from 2007 to the present.

Methods:The prognostic variables effecting overall survival (OS) were examined in a unique prospectively collected cohort of 168 advanced stage MF and SS patients evaluated at MD Anderson Cancer Center (Houston,TX) from 2007 to 2014. Kaplan–Meier estimates were used to determine median OS, progression-free survival (PFS), and disease-specific survival (DSS). Cox proportional hazards regression model assessed prognostic factors.

Results: Advanced patients included 97 MF (58%) and 71 SS (42%) patients with 106 (63%) males and 62 (37%) females. The median survival was 2.47 years (95% CI: 1.85 to 3.30). The range of the OS time was 7.21 years. The one-year survival rate was 76.9% (std error: 3.5%). The two-year survival rate was 57.2% (std error: 4.4%). The five-year survival rate was 30.9% (std error: 5.7%). The seven-year survival rate was 13.3% (std error: 9.9%). There were 79 (47%) deaths from any cause and 89 (53%) were alive at the end of analysis. Median OS for MF was 2.47 yrs and for SS was 2.19 yrs. The median OS for patients with large cell transformation (LCT) was 2.19 yrs, similar to OS of SS patients. Median overall survival of patients > 65 years was 1.73 years compared to 4.36 years in patients < 65 yrs of age (p=.0005). In patients with nodal disease, the median OS for N3 was 1.09 yrs, N2; 0.79 yrs compared to 2.90 yrs in Nx patients (p= <0.0001). DSS for MF was 2.85 yrs; SS was 3.15 yrs. Most patients died from disease: stage IVB 47%, IIB 38% vs stage III only 9%. In patients with various levels of blood involvement, median OS with B2 (>1000 SS) was 2.19 yrs and B1 (< 1000 and > 250) was 2.56 yrs. In the median OS and DSS for patients with a positive clone in the blood was 1.09 and 1.55 yrs respectively. In patients without a clone in blood, median OS and DSS were 2.09 and 4.36 yrs and not clinically significant. Elevated LDH levels were clinically significant p=0.04 with median OS 2.47 yrs. Expression of CD30 or CD25 was not significant for any of the two survival outcomes. Of 168 patients, 115 were treated with systemic therapies: including extracorporeal photopheresis (ECP), retinoids, interferons, targeted monoclonal antibodies, chemotherapy, total body skin electron beam, and stem cell transplant. The overall response rate (ORR) for all systemic therapies was 46% (n=52/115) with a complete response (CR) of 9% (n=10), partial response (PR) was 37% (n= 42) and 38% (n=44/115) had progressive disease (PD). ORR with ECP was 41% (n=30/74), SCT was 97% (n=16/17), retinoids was 30% (n=19/63). The ORR for single agent chemotherapy was 18% (n=20/112), multiple agent chemotherapy was 11% (n=12/112).

Conclusions:By univariate analysis, risk factors associated with disease progression or death included advanced age, lymph node involvement, and elevated LDH. The follow-up period was limited. The impact of treatments on prognosis has not been determined and apart from stem cell transplantation complete responses are rarely seen.