Clinical Trials and Efficacy Assessment in the Therapy of Cutaneous T Cell Lymphoma

Abstract

The ability of clinical trials to measure cutaneous T cell lymphoma (CTCL) has allowed physicians and regulatory reviewers to assess the response of the disease to experimental therapies. The goals of therapy are remission, palliation, and improvement of survival. Given the chronic nature of the disease, surrogate markers for survival are used in clinical trials. The surrogate markers and the validity of the surrogate markers used to date will be compared and contrasted. Tumor burden measurements by way of skin scoring are the parameters most commonly used to assess the response to therapy. Skin scoring systems have used global mapping, severity recording, or target lesions to assess any change in response to an intervention. The advantages and limitations of global and focal scoring are presented, along with examples of skin scoring systems for the five most recently completed trials for CTCL. Measures of palliation are performed via questionnaires. General and CTCL‐specific questionnaires have been developed that assess both discrete and global manifestations of the disease. Those measures of palliation that have been shown to correlate with skin scoring are presented for inclusion into future studies. In addition, study terms such as relapse and freedom from relapse can now be defined with reproducible molecular techniques. Every stage of CTCL warrants further clinical trials, and guidelines for future investigations are proposed.

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

“…29,30 However, assessing response to treatment is not necessarily straightforward. MF is an indolent condition with a long natural history and may not extend beyond the skin for many years.…”

“…7 This finding has necessitated the use of surrogate markers, such as the tumour burden measurements described by Heald, which can be used to assess the effects of treatment. 29 …”

Romidepsin in the treatment of cutaneous T-cell lymphoma

“…The RECIST criteria for solid tumors and the IWGG for lymphomas used in this trial give inaccurate estimations of the disease burden in skin or blood. The Severity-Weighted Assessment Tool (SWAT) score developed by Stevens et al34 uses the principle of grid-point counting and gives a more comprehensive, dynamic, and accurate measurement of the skin disease burden in MF 35. This score represents the product of the percentage total body surface area (%TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: SWAT = (patch %TBSA × 1) + (plaque %TBSA × 2) + (tumor or ulcer %TBSA × 3) within 12 body regions.…”

Clinically significant responses achieved with romidepsin across disease compartments in patients with cutaneous T-cell lymphoma

“…Disease assessments were performed for skin, lymph nodes and blood involvement. The extent of disease in the skin was determined using the Severity-Weighted Assessment Tool (SWAT) [ 30 , 31 ] and erythroderma score [ 18 , 32 ]. Nodal involvement was measured with the Response Evaluation Criteria In Solid Tumors (RECIST) methodology [ 33 ], and blood involvement was measured by determining the absolute count and percentage of circulating malignant T cells (Sézary cells) primarily via flow cytometry (CD4+/CD7− and/or CD4+/CD26− immunophenotype).…”