Extracorporeal photopheresis has significant therapeutic value in patients with Sezary syndrome, particularly when used early, Peter Mac-led research has found.

Based on the results of their international observational study, they also say combination therapies should be preferred over monotherapies for these patients and are associated with fewer treatment changes.

Some 178 Sezary patients in three countries (73% de novo, 27% secondary) were included, receiving 721 lines of systemic therapy, with a median follow-up of 56.9 months.

Given the multi-line treatment journeys of such patients, the main measure of clinical benefit was time-to-next-treatment (TTNT), which provided a robust, objective measurement of efficacy, according to the researchers.

This was relatively short across all first-line therapies (median 5.4 months), but combination therapies had double the median TTNT compared to monotherapies at 10 vs five months.

In addition, later delivery of combination therapies was associated with a shorter clinical benefit, with median with median TTNT reduced to 6.2 and 2.2 months for midline (2nd-4th line) and late line (≥5th line), respectively (p<0.001).

Reporting their findings in blood advances (link here), the investigators noted that international guidelines gave no preference to the sequencing of treatments in SS.

As a result, management approaches varied, even between experts at large institutions, they said.

“We report that in the first-line setting, retinoid monotherapy and extracorporeal photopheresis-based combination therapies were the two most commonly prescribed therapies, however, together only constituted approximately one third of the total of first-line therapies,” they wrote.

“Multi-line treatment journeys were confirmed for these patients: the median number of treatment lines received was four (range, 1-16). Excluding non-systemic therapies, the median number of systemic treatments received was three, with some patients receiving up to 14 lines of systemic therapy.”

“Retreatment with the same therapy was also common.”

The findings also underscored the importance of extracorporeal photopheresis in Sezary syndrome treatment. Delivered alone at first, this achieved a median TTNT of eight months, rising to 9.8 months when used in combination, the researchers found.

“Beyond extracorporeal photopheresis, we postulate that the observed prolongation of disease control with combination therapy most likely reflects the combined symptomatic and disease control benefits, which in turn outweigh any additional toxicity arising from a need to intensify treatment regimens,” they added.

“Not suprisingly, we found that TTNT of combination therapies is influenced by the timing of treatment delivery, with later delivery in the treatment sequence being associated with shorter duration of clinical benefit.”

The study also examined use of allogeneic stem cell transplant (AlloSCT), currently the only curative treatment option for Sezary syndrome patients, according to the authors.

Despite this, only 13.5% of the cohort received such treatment, likely reflecting the risks of significant treatment-related morbidity and mortality that precluded the majority of Sezary syndrome patients with advanced age or comorbidities from accessing it, they said.

Nevertheless, the data demonstrated an “impressive” TTNT, with predicted freedom from next line of treatment measuring 80.1% at 1 year and 72.1% at 2 years.

“However, given the increasing availability of monoclonal antibody-based treatments, and the ongoing development of novel therapies, the dilemma of optimal treatment sequencing of AlloSCT remains unresolved,” they added.