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

Abstract

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, from three quaternary centers, examines patterns of clinical care and therapeutic benefit as measured by TTNT. TTNT was calculated for monotherapies and combination therapies, with consideration given 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. First-line, the most common 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=0.004), respectively. Later delivery of combination therapies was associated with shorter clinical benefit, with median TTNT reduced to 6.2 and 2.2 months for midline (2nd-4th line) and late line (>4th line), respectively (p<0.001). First-line, ECP-containing treatments were associated with longer median TTNT compared to non ECP-containing treatments: 9.0 vs 4.9 months (p=0.007). 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 patients with SS, and favor early inclusion of ECP in the treatment algorithm for those who can access it.

Sézary Syndrome in West Sweden: Exploring Epidemiology, Clinical Features, and Treatment Patterns in a Registry-Based Retrospective Analysis

“…In our study, retinoids were primarily used as first-line therapy, comprising 65% of cases, and were commonly employed across all treatment regimens, either alone (45%) or in combination with ECP (58%). TTNT for all retinoids was 5.85 months, which was higher than the 4.4 months reported in another study [ 14 ]. When retinoids were used in combination therapy with ECP, the TTNT was 6.38 months, and in combination with IFN-α, this extended to 14.14 months.…”

“…The initial management of SS patients varies, as there are several treatment options [ 14 , 42 ]. The median duration of all treatments among our patients was 5.88 months, which is consistent with previous reports [ 14 , 43 ].…”

“…SS follows a more aggressive course than other variants of CTCLs, and it is also incurable. Fortunately, there are a number of treatment options that can ameliorate symptoms and stop disease progression, though many of these yield only partial responses (PRs) of brief duration [ 14 ]. Skin colonization with Staphylococcus aureus can contribute to disease flares and has been described in patients with SS [ 15 , 16 , 17 , 18 , 19 , 20 ].…”

Mogamulizumab Combined with Extracorporeal Photopheresis as a Novel Therapy in Erythrodermic Cutaneous T-cell Lymphoma

“…Research suggests that combining ECP with complementary therapies may lead to better response rates [ 12 , 31 ]. Also, it appears that patients benefit from early inclusion of ECP to their treatment regime [ 17 ].…”

“…Additionally, Campbell et al demonstrated that first-line combination therapies have a longer time to next treatment (TTNT) than monotherapies and that patients benefit from an early inclusion of ECP in their therapeutic algorithm [ 17 ].…”