Safety of Concurrent Systemic Therapy and Total Skin Electron Therapy in Cutaneous T-Cell Lymphoma

PURPOSE: To evaluate the safety and outcomes of total skin electron therapy (TSET) delivered with concurrent systemic therapy (CS) for cutaneous T-cell lymphoma (CTCL). METHODS: We retrospectively identified CTCL patients (including Sézary syndrome and mycosis fungoides) receiving TSET from 2013 to 2023. Acute toxicities were graded per CTCAE v5.0 and defined as new or worsened (N/W) from baseline. Cutaneous response was assessed at 2-8 weeks and 6 months post-TSET. Analyses of toxicity and response were performed per TSET course and classified as CS if any systemic agent was administered during treatment. Survival outcomes were estimated using Kaplan-Meier methods in per-patient analyses using one index course per patient, with time measured from the start of TSET. RESULTS: A total of 121 TSET courses were analyzed, including 75 (62%) with CS and 46 (38%) without concurrent systemic therapy (NCS). Median follow-up was 21 months overall and longer for CS courses (28 vs. 16 months; P = .019). Nearly all courses experienced ≥1 N/W toxicity, most of which was low grade. High-grade toxicities occurred in 13% of CS and 26% of NCS courses (P = .080), with no grade ≥4 events. Overall, toxicity burden and symptom outcomes were similar between groups. Toxicity severity appeared comparable across commonly used systemic therapy classes; one patient receiving concurrent methotrexate experienced disproportionate toxicity. Early overall response rates at 2-8 weeks were 90% (CS) and 92% (NCS) (P = .138). In per-patient analyses, median progression-free survival was 8.61 versus 6.08 months (log-rank P = .325), and 24-month overall survival was 85.7% versus 68.3% (log-rank P = .098) for CS and NCS, respectively. CONCLUSIONS: TSET can be delivered safely with most commonly used CS therapies in CTCL.