A comparative analysis of histone deacetylase inhibitors for the treatment of mycosis fungoides and Sézary syndrome

Papps, Theone; McCormack, Chris; Buelens, Odette; Weyden, Carrie van der; Twigger, Robert; Campbell, Belinda A.; Dickinson, Michael; Prince, H. Miles

doi:10.1111/bjd.18522

Cited by 5 publications

(6 citation statements)

References 7 publications

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“…TTNT provides a reliable, simple, patient-centric, surrogate end point for duration of clinical benefit, with established use in CTCL. 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 TTNT encompasses both the clinical response and tolerability of the treatment as experienced by the patient; it is a particularly useful end point to measure the durability of clinical benefit of treatments in the real-world setting, providing an objective measure of therapeutic benefit that may be applied retrospectively. 27 , 28 TTNT is defined as the time from commencement of 1 therapy to the commencement of the subsequent line of therapy.…”

Section: Introductionmentioning

confidence: 99%

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

Campbell,

Dobos,

Haider

et al. 2023

Blood Advances

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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.

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Section: Introductionmentioning

confidence: 99%

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

Campbell,

Dobos,

Haider

et al. 2023

Blood Advances

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“…Few studies have directly compared the efficacy and safety profiles of HDACis in patients with MF/SS. A retrospective study compared the TTNT for romidepsin, vorinostat, and panobinostat in patients with MF/SS and reported that there were no significant differences between HDACi therapies, as the overall median TTNT was 5.5 months ( 50 ).…”

Section: Histone Modification In Ctclmentioning

confidence: 99%

Epigenetics in the Pathogenesis and Treatment of Cutaneous T-Cell Lymphoma

Zhang

2021

Front. Oncol.

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Cutaneous T-cell lymphomas (CTCLs) comprise a group of heterogeneous diseases involving malignant T cells. The pathogenesis and etiology of CTCL are still unclear, although a large number of genetic and epidemiological studies on CTCL have been conducted. Most CTCLs have an indolent course, making early diagnosis difficult. Once large-cell transformation occurs, CTCL progresses to more aggressive types, resulting in an overall survival of less than five years. Epigenetic drugs, which have shown certain curative effects, have been selected as third-line drugs in patients with relapsing and refractory CTCL. Many studies have also identified epigenetic biomarkers from tissues and peripheral blood of patients with CTCL and suggested that epigenetic changes play a role in malignant transformation and histone deacetylase inhibitor (HDACi) resistance in CTCL. Single-cell sequencing has been applied in CTCL studies, revealing heterogeneity in CTCL malignant T cells. The mechanisms of HDACi resistance have also been described, further facilitating the discovery of novel HDACi targets. Despite the heterogeneity of CTCL disease and its obscure pathogenesis, more epigenetic abnormalities have been gradually discovered recently, which not only enables us to understand CTCL disease further but also improves our understanding of the specific role of epigenetics in the pathogenesis and treatment. In this review, we discuss the recent discoveries concerning the pathological roles of epigenetics and epigenetic therapy in CTCL.

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“…Over the past 5 years, TTNT has been utilised and endorsed as a surrogate marker for DOCB in clinical studies of CTCL [2][3][4][5][6][7][8]. TTNT represents the interval from commencement of one treatment to initiation of the next line of therapy.…”

Section: Ttnt In Ctclmentioning

confidence: 99%

“…However, TTNT provides a clinically meaningful and tangible endpoint in the retrospective setting. A recent retrospective study of three HDACi (infusional romidepsin, oral vorinostat, and oral panobinostat) in patients with multiply-relapsed MF/SS, reported an overall median TTNT of 5.5 months (range, 1-124) with no significant differences found in TTNT between the three agents [4]. This study demonstrated the usefulness of TTNT as a surrogate endpoint for DOCB: TTNT considered not only the duration of disease control from the HDACi but also the patient experience, incorporating differences in patient compliance and tolerability which may have arisen from differing modes of administration and toxicity profiles.…”

Section: Ttnt In Published Retrospective Studies In Ctclmentioning

confidence: 99%

“…Furthermore, TTNT offers a better reflection of the patients' treatment experiences than conventional disease-related endpoints by incorporating the time course of treatment tolerability and patient compliance. In clinical studies of CTCL, TTNT is used as an addition to conventional evaluation criteria and also as a stand-alone assessment of duration of treatment efficacy [2][3][4][5][6][7][8], but to date no standardised definition has been agreed. Herein, we review the use of TTNT in the published CTCL literature, and propose a new standardised definition that accounts for the unique characteristics and challenges of CTCL.…”

Section: Introductionmentioning

confidence: 99%

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Time to Next Treatment as a Meaningful Endpoint for Trials of Primary Cutaneous Lymphoma

Campbell

Scarisbrick

Kim

et al. 2020

Cancers

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Time to next treatment (TTNT) is an emerging endpoint in clinical studies of primary cutaneous T-cell lymphomas (CTCL), with utility as a surrogate marker for the “duration of clinical benefit”. TTNT provides a highly clinically meaningful endpoint that uniquely reflects not only the duration of treatment efficacy on disease and symptom control, but also incorporates the patient experience by accounting for patient compliance and tolerance to the studied therapy(s). Given the distinct challenges of pin-pointing the exact date of progression in patients with multi-compartmental CTCL, TTNT overcomes many of the shortcomings of conventional, disease-focused, clinical endpoints in primary CTCL research. Although widely accepted in clinical research for numerous other incurable malignancies, TTNT currently lacks a standardised definition. In this paper, we describe the value of TTNT as a clinical endpoint, review the applications of TTNT in primary CTCL research, and propose a standardised definition of TTNT to be applied in future clinical research of primary CTCL therapies.

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A comparative analysis of histone deacetylase inhibitors for the treatment of mycosis fungoides and Sézary syndrome

Cited by 5 publications

References 7 publications

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

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

Epigenetics in the Pathogenesis and Treatment of Cutaneous T-Cell Lymphoma

Time to Next Treatment as a Meaningful Endpoint for Trials of Primary Cutaneous Lymphoma

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