Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkins lymphomas (NHLs) that predominately affect the skin, causing potentially immense suffering due to itching, skin pain, hair loss, and chronic non-healing wounds (1). Mycosis fungoides (MF) and Sézary Syndrome(SS) make up the majority of CTCLs. There is currently no agreed upon COS specific to Health-Related Quality of Life (HRQoL) in cutaneous T cell lymphoma (CTCL). CTCL is unique in that it is a primarily skin-based disease, unlike all other NHL’s which are systemic/internal cancers with little if any outward impact on the skin, however, it also has the potential to cause advanced symptoms and even death, unlike many skin diseases. Early studies investigating HRQoL in patients with CTCL demonstrated that patients with CTCL have significant impacts on QoL across numerous domains, with a majority experiencing health distress and worrying about dying from their disease(2). A COS specific to CTCL is critical and needed.
The HARMONY and HARMONY PLUS COS protocol published in 2022 aims to include all “NHLs” in its focus on response outcomes as well as some HRQoL outcomes. Lumping CTCL with all NHLs will likely miss the mark for many HRQoL outcomes relevant to CTCL. Although CTCL is classified as a NHL, this subgrouping of patients is rarely utilized in therapeutic clinical trials, particularly when considering the vast majority of patients with CTCL who have early/indolent disease that behaves much more like a chronic skin condition. Therefore, attempts to lump these fundamentally different patients, along with systemic lymphomas will almost certainly exclude many core outcomes significant to this patient group (for example itching, skin burning, wounds, and skin pigment changes).
The ongoing ARMFUL COS project focuses on developing a COS for workup, monitoring, and treatment of MF in pediatric populations. This protocol is limited in scope of disease, patient population, and is not focused on HRQoL, thus is not relevant to the goals of our intended project.
For our proposed project, we do not aim to change or focus on response outcomes, or workup for the disease. This project is instead focused on developing a COS of Patient-Reported Outcome Measures (PROMs) for patient registries and interventional clinical trials for CTCL (MF/SS), and to identify a COS for clinical practice within the same group. These efforts will include input from patients with CTCL and providers who care for CTCL.
References:
1. Willemze R, Cerroni L, Kempf W, et al. 2018 WHO-EORTC classification update. Blood.2019;133(16):1791.
2. Demierre MF, Gan S, Jones J, Miller DR. Significant impact of cutaneous T-cell lymphoma on patients' quality of life: results of a 2005 National Cutaneous Lymphoma Foundation Survey. Cancer. 2006;107(10):2504-2511.
3. Lang K, Bereczky T, et al. Pan-Stakeholder Core Outcome Set (COS) Definition for Hematological Malignancies within the Framework of Harmony and Harmony PLUS Projects. Blood 2022; 140 (Supplement 1): 5285–5287. doi: https://doi.org/10.1182/blood-2022-157549
Cecilia Larocca MD - Principal Investigator - Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Dana-Faber Cancer Institute, Boston, MA, USA
Michi Shinohara MD - Department of Dermatology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA, USA
Nilu Khan MD – Department of Hematology and Oncology, City of Hope, Durante, CA, USA
Ellen Kim MD – Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
Rosanne Ottevanger MD – Department of Dermatology, University of Leiden, Leiden, Netherlands
Julia Scarsbrick MBChB, FRCP, MD - Department of Dermatology, University Hospitals Birmingham NHS Foundation, Boston, MA, USA
Elisa Olsen MD - Departments of Dermatology and Medicine, Duke University, Durham, NC, USA
Marianne Tawa NP - Department of Dermatology, Dana-Faber Cancer Institute, Boston, MA, USA
Susan Thorton – Cutaneous Lymphoma Foundation, Warren, MI, USA
Christina Asare - Department of Dermatology, University of Washington, Seattle, WA, USA
Jennifer Chen MD - Department of Dermatology, University of Washington, Seattle, WA, USA
Disease Category: Cancer
Disease Name: Cutaneous T-Cell Lymphoma
Age Range: 18 - 120
Sex: Either
Nature of Intervention: Any
- Clinical experts
- Conference participants
- Consumers (caregivers)
- Consumers (patients)
- Families
- Governmental agencies
- Methodologists
- Patient/ support group representatives
- Pharmaceutical industry representatives
- Researchers
- Service providers
- Statisticians
- COS for clinical trials or clinical research
- COS for practice
- Consensus conference
- Consensus meeting
- Delphi process
- Focus group(s)
- Interview
- Literature review
- Survey
- Systematic review
The following project is intended to involve patients, a multidisciplinary group of health care professionals, patient advocacy groups, industry representatives, and methodologists (and government agencies) to assist in the generation of HRQoL domains related to CTCL and/or the consensus process. This is the first and only initiative to include a comprehensive group of stakeholders.
Participants will be categorized as either patients or health care professionals for ease of analysis. We aim to have a 1:1 ratio of patients to health care professionals. Patients will be enrolled via contact with resident CTCL expert provider and the patient research partner (Cutaneous Lymphoma Foundation). Patients must have a confirmed diagnosis of CTCL by dermatology or medical oncology to be deemed eligible for participation. Providers will be enrolled via professional organizations (e.g. the United States Cutaneous Lymphoma Consortium). Providers with expertise in CTCL care (a clinical background with at least (5) years of experience with CTCL (may include residency training) and at least (20) patients treated per year will be deemed eligible to participate. All participants must have internet access and be English speaking.
The development of a CTCL-specific core domain set will employ multiple strategies, a systematic review of the literature, qualitative studies/focus groups, items generated by HCPs, and a Delphi consensus process as follows:
An updated systematic literature review of patient reported outcome measures, qualitative studies of CTCL patients and caregivers will be performed to identify relevant domains.
Qualitative studies/focus groups - A group of patients that have been identified as underrepresented in MF/SS patient populations (eg. Patients who identify as non-white or Hispanic) will be purposefully recruited and interviewed and analyzed via thematic analysis to identify significant concepts related to symptoms and effects on life that are relevant to patients with CTCL. Supplemental focus group interviews will be conducted if needed to improve the item-generating process.
Items generated by HCPs – Healthcare providers will be recruited to complete an electronic survey. The survey will require participants to list all items that they consider important or relevant to CTCL (eg. items related to aspects or treatment of the disease).
A preliminary list of potential items will be produced and conceptualized by combining the results from the systematic reviews, qualitative studies, and the HCPs’ item generation survey.
Stakeholders will be invited to participate in the Delphi consensus process to achieve consensus on the core domain set. An anonymous Delphi approach will be used. Participants are asked to rate the importance of the listed items. Participants will also be allowed to add additional items that they think are missing together with a scoring for the added items. A minimum of two e-Delphi rounds is planned, with two “face-to-face” consensus meetings (in-person or via teleconferencing) occurring after each e-Delphi rounds.
The steering group will consider all elicited feedback from participants and adjust domain set if there is majority consensus within the group. Statistical corrections for multiple significance testing and false positive findings will be undertaken.