A collaboration of international experts is tackling the challenges involved in understanding and managing the treatment of cutaneous lymphomas. The Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study from the Cutaneous Lymphoma International Consortium brings together experts from various smaller organizations in Europe, Israel, Japan, Brazil, Australia, and the United States to collaborate on an unprecedented level to acquire large-sample data on this group of rare skin lymphomas.1
To be able to use all the great scientific advances in this area, we need to have data on large numbers of patients and to work together. Bringing together an international consortium will have a global impact.— Youn Kim, MD
Previous efforts to classify cutaneous T-cell lymphomas have been hampered by small numbers of patients in individual regions of the world. The hope is that this large-scale, global effort will move the field forward and standardize diagnosis, staging, and research on treatments.
The Cutaneous Lymphoma International Consortium’s first large-scale research project is the PROCLIPI study, designed to collect and share data on cutaneous T-cell lymphoma, which is characterized by heterogeneous clinical presentation, histopathology, and molecular features. PROCLIPI has undertaken separate prospective studies on early-stage and advanced-stage mycosis fungoides, a common type of cutaneous T-cell lymphoma.
“To be able to use all the great scientific advances in this area, we need to have data on large numbers of patients and to work together. Bringing together an international consortium will have a global impact,” said Youn Kim, MD, of Stanford University School of Medicine, Stanford, California, an expert in cutaneous lymphoma, founding member of the Cutaneous Lymphoma International Consortium, and the global co-leader of the PROCLIPI project.
The PROCLIPI studies aim to develop a means of identifying high-risk patients with poor outcomes, with the goal of optimizing management to improve survival and quality of life in mycosis fungoides/Sézary syndrome patients.— Julia Scarisbrick, MD
At the recent 3rd World Congress of Cutaneous Lymphomas, Julia Scarisbrick, MD, of the University of Birmingham, United Kingdom, and a prime mover in cutaneous lymphoma and the Cutaneous Lymphoma International Consortium, brought attendees up-to-date on separate studies of PROCLIPI in early and advanced cutaneous T-cell lymphoma.2
Current staging systems for cutaneous T-cell lymphoma are suboptimal and do not accurately stratify patients according to survival. Dr. Kim and colleagues are seeking to emulate the model of the International Prognostic Index (IPI) for aggressive non-Hodgkin lymphoma and create a staging system that identifies risk factors for advanced-stage mycosis fungoides and Sézary syndrome and categorizes patients according to risk level to guide subsequent treatment approaches.
PROCLIPI investigators are prospectively collecting clinical, pathologic, laboratory, and molecular data from patients with cutaneous T-cell lymphoma in their respective countries. Each participating institution will have its own biobank, but data collection will be done in a standardized way.
“When an investigator proposes a project of discovery, participants will have samples at their own sites, and projects can be realized,” Dr. Kim said. “This will serve as the foundation for more impactful, large-scale clinical and translational research in cutaneous T-cell lymphoma,” she noted.
Developing a Prognostic Model
Patients entered in PROCLIPI studies had mycosis fungoides or Sézary syndrome, two common entities of cutaneous T-cell lymphoma. Dr. Scarisbrick and Dr. Kim are leading the major international collaboration for developing a prognostic index in early-stage mycosis fungoides/Sézary syndrome.
Prior to launching the prospective study, the Cutaneous Lymphoma International Consortium conducted and published a retrospective study in 2015 and found that prognostic factors in early-stage cutaneous T-cell lymphoma were different from those in later-stage disease. Among 1,275 patients from 29 centers, the study identified 4 independent prognostic factors associated with poor survival: stage IV disease, age older than 60 at diagnosis, increased serum lactate dehydrogenase, and large cell skin transformation.
With these factors used in a prognostic model, patients with stages IIB to IVB disease could be categorized into three risk groups as low risk (0–1 of these risk factors), intermediate risk (2 risk factors), or high risk (3–4 risk factors), with significantly different 5-year survival rates: 68%, 44%, and 28%, respectively. The risk category did not necessarily correlate with disease stage. This unprecedented international study was published in the Journal of Clinical Oncology.1 This retrospective study confirmed the feasibility of conducting large-scale international projects and served to refine the design for the prospective study, PROCLIPI.
Dr. Scarisbrick is now leading the major international PROCLIPI study in early-stage mycosis fungoides, including patients with stages IA through 2A disease, and has currently recruited more than 400 patients in the first year. “Mycosis fungoides has orphan disease status, and this is already the largest study ever of early-stage patients,” she revealed.
The cutoff of stage IIA for early stage was selected, because this group tends to have a good prognosis, but a small number have poor outcomes, with 10-year survival for this group being 77% and for stage IIB, just 21%, Dr. Scarisbrick explained.
International Collection of Data
The Cutaneous Lymphoma International Consortium participants will collect data on the following aspects of each patient: clinical, pathologic, nodal, hematologic, genotype, treatment, and biobank samples. Dr. Scarisbrick invited audience members and the international cutaneous lymphoma community to join forces and enter their patients’ data on the Web-based sites. The PROCLIPI data system has built-in intelligence to stage patients from the data and to cross check for accuracy.
Rein Willemze, MD
“The study relies on collaboration and international participation for success,” she said. Thus far, 432 patients have enrolled from 34 centers in 14 countries spanning 3 continents; 77% have early-stage disease, and 23% have advanced cutaneous T-cell lymphoma. Of them, 197 early-stage patients have gone through virtual central clinical/pathologic review, led by Rein Willemze, MD, of the Leiden University Medical Center, the Netherlands: 159 passed (137 classical mycosis fungoides, 22 folliculotropic mycosis fungoides), and 38 failed. Of the failures, 6 went on the have real-time central review and passed.
The investigators have noted that the median age differs from stage IA (median, 55 years) to stage IB (median, 59 years). The male-to-female ratio for early-stage disease is 1.6:1. Median duration of mycosis fungoides lesions prior to diagnosis is longer in stage IB than stage IA disease, but there is no difference in the duration of mycosis fungoides lesions prior to diagnosis in early vs late disease, confirming that advanced disease is a different and more aggressive form of cutaneous T-cell lymphoma.
PROCLIPI investigators are analyzing hematologic parameters and lymph node data, trying to collect the number of positive lymph nodes, sites involved, and the largest node at each site in patients with all stages of mycosis fungoides. They hope to more accurately measure lymph node burden than with the current staging system, which simply recognizes the pathology of a single node.
Evaluating Treatment Effects and Quality of Life
The Cutaneous Lymphoma International Consortium study is evaluating treatment effects on disease and quality of life to determine which treatments are beneficial. Data on treatment include the type of treatment, the date started, the date stopped, and no treatment.
The study of early-stage disease has treatment data on 229 patients thus far; 120 were stage IA, 99 were stage IB, and 10 were stage IIA. Based on first-line treatment, slightly less than one-third (29.4%) were treated with topical steroids, and the response rate was 63%. Nearly one-third (32.8%) were treated with phototherapy, and the response rate was 77%. Oral retinoids were used in 7.7%, with a response rate of 67%. Overall, 66% of patients responded to therapy.
“The PROCLIPI studies aim to develop a means of identifying high-risk patients for poor outcome and optimizing management, with the goal of improved survival and quality of life in mycosis fungoides/Sézary syndrome patients,” Dr. Scarisbrick concluded. ■
Disclosure: Dr. Kim has received consulting fees from Seattle Genetics, Takeda Pharmaceuticals, and Millennium Pharmaceuticals and is on the steering committee for Takeda Pharmaceuticals and Millennium Pharmaceuticals. Dr. Scarisbrick reported no potential conflicts of interest.
1. Scarisbrick JJ, Prince HM, Vermeer MH, et al: Cutaneous Lymphoma International Consortium study of outcome in advanced stages of mycosis fungoides and Sézary syndrome: Effect of specific prognostic markers on survival and development of a prognostic model. J Clin Oncol 33:3766-3773, 2015.
2. Scarisbrick J, Quaglino P, Vermeer M, et al: Prospective cutaneous lymphoma international study (PROCLIPI) in early stage mycosis fungoides. 3rd World Congress of Cutaneous Lymphomas. Abstract C-02. Presented October 26, 2016.