Real-world treatment patterns in patients with Sézary syndrome in the United States and the impact of Covid-19

Background: Sézary syndrome (SS) is an aggressive type of cutaneous T-cell lymphomas (CTCL). Due to its low prevalence, there are limited data on real-world treatment patterns of currently available SS therapies. Furthermore, recent approvals of new agents for patients with CTCL as well as COVID-19 likely impacted real-world treatment patterns. Objective: To examine real-world treatment patterns and the impact of COVID-19 among SS patients treated in 2018-2020 in the US. Methods: Patients with public or private insurance in the 2018-2020 Symphony Health Solutions database were classified into 3 groups: ≥1 diagnosis of SS (ICD-10-CM code: C84.1x) in 2018, 2019, and 2020, respectively. Patient characteristics and treatment patterns for all therapies recommended by the National Comprehensive Cancer Network guidelines version 2.2021 were examined: systemic therapy (e.g., extracorporeal photopheresis (ECP), parenteral, or oral agents), skin-directed therapy (SDT, e.g., topical, local radiation, total skin electron beam therapy, or phototherapy) and bone marrow transplant. The impact of COVID-19 was assessed via quarterly analysis. National drug codes, current procedural terminology and healthcare common procedure coding system codes were used to identify all treatments. Results: The analyses included 869, 882, and 853 SS patients in 2018, 2019, and 2020, respectively (mean age: 66.3, 66.9 and 67.3 years;male: 54.4%, 54.8%, and 55.6%). Overall, systemic therapy increased from 2018 to 2020 (41.8% to 46.5%), with increased parenteral (20.7% to 28.7%) but decreased ECP (17.0% to 13.5%) usage. SDT increased from 2018 to 2020 (48.9% to 52.9%), with increased topical (42.3% to 48.3%) but decreased phototherapy (6.3% to 4.1%) usage. ECP, mogamulizumab, and bexarotene were the most prescribed systemic therapies in 2019-2020, with mogamulizumab being the only one with increased usage over time. Quarterly analysis showed a decreasing ECP from Q1 to Q4 within each year, with a notable drop in Q2 2020. For parental systemics, there was an increasing trend in 2019 and 2020, but utilization in Q4 2020 was lower than that of Q3 2020. For oral systemic, there was a notable drop in Q2 2020 but an increased trend in Q3-Q4 2020. Conclusions: This claims analysis indicated increased use in systemic and SDT among SS patients in 2018-2020. The quarterly analysis indicated that the drop in ECP and oral systemic usage in Q2 2020 coincided with the onset of the pandemic, but there was a stable use of parenteral systemic during 2020.

Real-World Treatment Patterns Among Patients with Mycosis Fungoides and Sézary Syndrome in the United States between 2018 and 2020

Objectives: Mycosis Fungoides (MF) and Sézary syndrome (SS) are the two most common subtypes of cutaneous T cell lymphomas. Given their low prevalence, real-world treatment patterns of existing and newly approved therapies for MF and SS remain unknown, especially during the COVID pandemic. This study examined treatment patterns among patients with MF or SS between 2018-2020 in the United States. Methods: Patients in the Symphony Health Solutions database were classified into 6 groups: ≥1 MF diagnosis (no SS diagnosis) in 2018, 2019, and 2020, and ≥1 SS diagnosis in 2018, 2019, 2020, respectively. Utilization of treatments recommended by the current National Comprehensive Cancer Network guidelines was examined: skin-directed therapy (SDT;topical, local radiation, total skin electron beam therapy, or phototherapy), systemic therapy (extracorporeal photopheresis [ECP], parenteral, or oral), and bone marrow transplant (BMT). Results: Overall(mean age;male), 10,527(62.9 years;54.6%), 10,078(63.2 years;54.3%) and 9,414(63.2 years;53.9%) patients had ≥1 MF diagnosis and 869(66.3 years;54.4%), 882(66.9 years;54.8%) and 853(67.3 years;55.6%) patients had ≥1 SS diagnosis in 2018, 2019 and 2020, respectively. From 2018-2020, 56.1-56.6% of MF (SDT 52.1-52.5%;systemics 12.1-13.5%;BMT 0.1-0.2%) and 64.6-68.8% of SS patients (SDT 48.9-52.9%;systemics 41.8-46.5%;BMT 0.8-1.5%) had ≥1 treatment claims. Among MF patients with any systemic therapies, bexarotene was the most common in 2018 (28.1%) and 2019 (27.5%), methotrexate in 2020 (27.2%), and mogamulizumab (2018 MF/SS approval) the 6th most common in 2019 (6.8%) and 2020 (6.6%). Among SS patients with any systemic therapies, ECP was the most common in 2018 (40.8%) and 2019 (33.3%), and mogamulizumab in 2020 (29.2%). Conclusions: Using claims from 2018-2020, approximately half of MF and SS patients had SDT each year, without major change during the COVID pandemic. Since 2018 in SS, there was an increasing systemic usage, with increasing mogamulizumab but decreasing ECP usage.

Acute and sub-acute toxicity profile of ultra-hypofractionated low-dose total skin electron beam with two 4 Gy fractions for cutaneous T cell lymphoma.

PURPOSE: Low-dose total skin electron beam therapy (TSEBT) over 3 weeks has proved to be a safe and effective treatment for cutaneous T cell lymphomas (CTCL). In this prospective trial, we examined the feasibility of ultra-hypofractionated low-dose TSEBT regimen in two fractions with 4 Gy combined with systemic therapy to minimize the number of visits to radiation centers. PATIENTS AND METHODS: Six patients with mycosis fungoides (MF) or Sézary syndrome (SS) received TSEBT with a total radiation dose of 8 Gy in two fractions between April 2020 and June 2020. Patient and treatment characteristics, tumor burden, the impact on the quality of life using Skindex-29 questionnaires, and acute toxicities were analyzed. RESULTS: During TSEBT, all patients developed grade 1 toxicities while two patients developed grade 2 toxicities. One patient experienced sepsis. The most common adverse effects were erythema and edema. All grade 2 toxicities regressed after 4 weeks following TSEBT. Based on the reported symptoms measured by Skindex-29, we detected a significant reduction in total Skindex-29 score after 8 weeks of radiation (P = 0.03), particularly in the symptoms (P = 0.01) and emotional domains (P = 0.04). CONCLUSION: Ultra-hypofractionated low-dose TSEBT followed by systemic therapy seems to be a safe and feasible alternative to conventional fractionated TSEBT for patients with MF/SS. The skin tumor burden and the health-related quality of life have been significantly improved within 8 weeks following radiotherapy.

Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system.

Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10 % depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50 % maximal effective concentrations (EC50) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC50 1.13-2.01 µM). Bexarotene demonstrated the highest Cmax:EC50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.