International study of treatment efficacy in SS shows superiority of combination therapy and heterogeneity of treatment strategies.

Despite increasing availability of therapies, patients with Sezary syndrome (SS) commonly endure multi-line treatment journeys, mostly with partial responses of short duration. Measuring clinical benefit is challenging; time-to-next-treatment (TTNT) provides a robust, objective measurement of efficacy. This international observational study examines patterns of clinical care and therapeutic benefit as measured by TTNT. TTNT was calculated for monotherapies and combination therapies, with consideration to treatment line. 178 patients with SS (73% de novo, 27% secondary) were included, receiving 721 lines of systemic therapy, with median follow-up of 56.9 months. Across all lines, 58 different therapeutic regimens were prescribed (54 were systemic therapies) and classified into 17 treatment groups. The most common first-line treatments were extracorporeal photopheresis (ECP)-containing combination therapy (20%) and retinoid monotherapy (19%). Median TTNT for all first-line therapies was short (5.4 months). First-line, combination therapies had longer median TTNT than monotherapies, 10.0 vs 5.0 months (P = .004), respectively. Later delivery of combination therapies was associated with shorter clinical benefit, with median TTNT reduced to 6.2 and 2.2 months for mid-line (2nd-4th line) and late-line (≥5th line), respectively (P < .001). First-line ECP-containing treatments were associated with longer median TTNT than non-ECP-containing treatments, 9.0 vs 4.9 months (P = .007). For both ECP-monotherapy and ECP-containing combination therapy, significant reductions in TTNT were seen in later lines. These data suggest therapeutic benefit from first-line delivery of combination therapy for SS and favor early inclusion of ECP in the treatment algorithm for those who can access it.