Mycosis Fungoides-type Cutaneous T-cell Lymphoma Research Articles

Additional Findings of 18 F-AIF-FAPI-42 PET/CT in a Patient With Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma : Comparisons With 18 F-FDG PET/CT.

A 44-year-old woman presented with extensive skin patches and pruritus persisting for 3 years. Histopathological examination of the skin from the right abdomen confirmed mycosis fungoides-type cutaneous T-cell lymphoma. Staging PET with 18 F-FDG PET/CT) showed increased uptake in the skin on the right abdomen and left hip. Subsequently 18 F-FAPI-42 PET/CT revealed additional foci of abnormal uptake on the skin of the chest and back.

Mechlorethamine Hydrochloride Gel in the Treatment of Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma (MF-CTCL): A Focus on Patient Selection and Special Considerations.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL) and often has an indolent course, particularly for patients presenting with early-stage (patch/plaque) disease. Early-stage MF is primarily managed with skin-directed therapies. Topical mechlorethamine hydrochloride (nitrogen mustard [NM]) gel has increased tolerability compared to prior NM formulations, though contact dermatitis remains a common side effect. The addition of topical steroids can improve tolerability while maintaining the efficacy of NM gel. Real-world experience supports that NM gel also has a role in combination therapy and as adjunctive therapy in advanced-stage disease. Here we review factors that may influence patient selection for use of NM gel, including MF variants, special patient populations, cost effectiveness, and impact on quality of life for patients with MF.

Maintenance and Concomitant Therapy Use with Chlormethine Gel Among Patients with Stage IA/IB Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma (MF-CTCL): A Real-World Evidence Study.

Chlormethine (CL) gel is a skin-directed therapy approved for treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in the USA. MF-CTCL has a chronic clinical course, requiring long-term maintenance therapy with one or more therapies. This analysis describes real-world patterns of maintenance therapy and use of concomitant therapy with CL gel among patients with stage IA/IB MF-CTCL. In a US-based registry, MF-CTCL patients treated with CL gel were enrolled between 3/2015 and 10/2018 across 46 centers and followed for up to 2years. Patient demographics, clinical characteristics, CL gel treatment patterns, concomitant treatments, clinical response, and adverse events (AEs) were collected from medical records. Descriptive statistics are reported. Of the 206 patients with stage IA/IB MF-CTCL, 58.7% were male, and average age was 60.7 years with 4.6 years since diagnosis. Topical steroids, phototherapy, and topical retinoids were used concomitantly with CL gel in 62.6%, 26.2%, and 6.3% of patients, respectively. Most concomitant therapies (up to 85%) were started before CL gel initiation and, in about half of the cases (up to 57%), were used concurrently for ≥ 12months. Overall, 158 (76.7%) patients experienced partial response (PR) and 144 continued with maintenance therapy. After achieving PR, most patients (74.3%) kept the same maintenance therapy schedule, most commonly once daily. Of patients who had any skin-related AE (31.6%) or skin-related AEs associated with CL gel (28.2%), nearly half experienced CL gel treatment interruption and ~40% had a dosing reduction. The observed real-world treatment patterns were concordant with National Comprehensive Cancer Network (NCCN) guidelines. The study results suggest that continuing CL gel maintenance therapy and combining treatments with CL gel are common practice in the real-world setting, with most maintained on a stable dosing schedule. Careful management of AEs may help patients maintain long-term optimal dosing with less treatment interruptions and dosing reductions.

Chlormethine Gel (Ledaga)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses chlormethine gel (Ledaga), 160 mcg chlormethine per gram gel, in 60 g tubes, for topical application to the skin.
 Indication Proposed: For the topical treatment of mycosis fungoides-type cutaneous T-cell lymphoma in adult patients.

Chlormethine Gel (Ledaga)


 CADTH recommends that Ledaga should not be reimbursed by public drug plans for the treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in adult patients who have received prior skin-directed therapy.
 Although evidence from a clinical trial found that Ledaga was not inferior to chlormethine ointment, chlormethine ointment is not used in Canada. There was no evidence to show whether Ledaga works better than or similar to treatments for MF-CTCL that are currently used in Canada.
 There is an unmet need for treatments with fewer side effects, but it remains unknown whether Ledaga has fewer side effects compared with other treatments for MF-CTCL used in Canada.

Tre-P-01 - Concomitant use of steroids or phototherapy with chlormethine gel among patients with mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL): a real-world evidence study

<h3>Background:</h3> Chlormethine gel (also known as mechlorethamine) is a skin-directed therapy approved for the treatment of early-stage mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). In previously published data, topical steroids and phototherapy were found to be commonly used by patients treated with chlormethine gel. Post-hoc analyses on the PROVe study were carried out to describe the specific treatment sequence and timing of these concomitant therapies and chlormethine gel in a real-world setting among MF-CTCL patients. <h3>Methods:</h3> Data analyzed derives from the observational PROVe study using US-based registry of MF-CTCL patients treated with chlormethine gel and enrolled across 46 centers between March 2015 and October 2018. Patients were followed for up to 2 years after chlormethine gel initiation. Due to the observational nature of the study, patients had visits at irregular intervals. Information on patient demographics, medical history, clinical characteristics, ongoing treatments for MF-CTCL and response were collected. Concomitant use of chlormethine gel with topical steroids or phototherapy were assessed using treatment start and stop dates recorded in the registry, and descriptive statistics were calculated. <h3>Results:</h3> A total of 298 eligible patients were analyzed with a mean ± standard deviation (SD) age of 61±13 years. Approximately 60% were males, 69% had Stage IA/IB and their duration of MF-CTCL was 4.8±6.5 years at chlormethine gel initiation. A total of 186 (85%) reported concomitant use of topical steroids with chlormethine gel during the study period. Of these 186 patients, 138 (74%) patients were already using steroids prior to chlormethine gel initiation, 14 (8%) started chlormethine gel and steroids on same day and the remaining 34 (18%) added steroids later. A total of 81 (27%) reported concomitant use of phototherapy with chlormethine gel during the study period. Of these 81 patients, 67 (83%) patients were already on phototherapy prior to chlormethine gel initiation and the remaining 14 (17%) initiated phototherapy later. <h3>Conclusions:</h3> Among the patients with concomitant therapies, the majority had started steroids or phototherapy and then added chlormethine gel. These observations suggest that in real life settings, combination treatments are standard practice as physicians expect improved outcomes with an acceptable tolerability profile.

Tre-P-02 - Maintenance therapy with chlormethine gel among patients with mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL): a real-world evidence study

<h3>Background:</h3> Chlormethine gel is a skin-directed therapy approved in US for daily treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). Based on a previous study it has been observed that the alternative treatment schedules and the schedule changes may benefit patients by improving tolerability and response to treatment [1]. This study was carried out to better understand schedule changes before and after achieving partial response (PR) and effect of maintenance therapy i.e., continuing treatment with chlormethine gel after achieving PR, in a real-world setting among MF-CTCL patients. <h3>Methods:</h3> Data is derived from the observational PROVe study using US-based registry of MF-CTCL patients treated with chlormethine gel in combination with other treatments between March 2015 and October 2018. Patients were enrolled across 46 centers and were followed for up to 2 years. Information on patient demographics, clinical characteristics, treatments received for MF-CTCL (including chlormethine gel, topical steroids, phototherapy, radiation therapy, chemotherapy, retinoids and other topical). Responses were collected at enrollment and ongoing visits with no specific visit schedules or clinical assessments due to expected variability in practice patterns. Episodes of treatments with chlormethine gel with start date, stop date and schedule changes were recorded and analyzed. Partial response (PR) was defined as either ≥50% improvement in body surface area (BSA) at least once from gel initiation to the end of study participation or based on the clinical assessment of the physician. For those who achieved PR and following the date of PR, deepening response was defined as achieving either ≥10% additional improvement in BSA (i.e., 60% or more improvement in BSA after achieving 50% improvement at the time of PR) or achieving complete response based on the clinical assessment by physician. Descriptive statistics were reported for schedule changes and maintenance therapy with chlormethine gel. <h3>Results:</h3> Of 298 eligible patients with mean age 61±13 years, 60% were males, and 69% had clinical stage IA/IB. A total of 222 (75%) patients achieved PR following chlormethine gel initiation and during study period. Of these 222, 81% patients did not change their schedule prior to achieving PR and 61% were on a daily schedule immediately prior to PR. Of 203 patients receiving maintenance chlormethine gel post PR, 153 (75%) maintained, 29 (14%) reduced and 24 (12%) increased their dosing schedule in the post-PR period as compared to their schedule prior to PR. Of these 203, 53 (26%) later achieved deepening response. <h3>Conclusions:</h3> 75% of the patients received maintenance therapy with chlormethine gel in combination with other therapies and continued with the same schedule after PR. The study results suggest that continuing maintenance therapy and adjusting chlormethine gel dosing schedule may contribute to deepen treatment responses.

25971 Schedule frequency of chlormethine gel for patients with mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL): A real-world evidence study

Chlormethine gel (also known as mechlorethamine) is a skin-directed therapy approved for daily treatment of MF-CTCL. Previous reports (including Gilmore 2020) explored alternative treatment schedules and suggested schedule changes may benefit patients. Patterns of initial treatment schedule and subsequent changes for chlormethine gel in a real-world setting among patients with MF-CTCL were investigated in an observational US registry between March 2015 and October 2018. Clinical characteristics and treatment information were collected, with patients followed for up to 2 years after baseline, defined here as chlormethine gel initiation.

PRO25 Healthcare Resource Use in Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma: Results from a UK-Based Clinician Questionnaire

PRO25 Healthcare Resource Use in Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma: Results from a UK-Based Clinician Questionnaire

PRO140 Health-Related Quality of Life Associated with Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma Patients: Determination of Utility Values from a UK-Based Clinician Questionnaire

Utility studies quantify the impact of disease on patients’ health-related quality of life (HRQoL). In rare diseases particularly, utility data are often limited. Where direct elicitation of data from patients is unfeasible, indirect methods are required to determine health state utility values (HSUVs). Here, we present indirect elicitation of HSUVs for patients with mycosis fungoides (MF), a rare skin lymphoma characterised by painful, itchy skin patches and plaques, which can progress into tumours and may involve blood, lymph nodes and viscera. Twelve distinct vignettes were prepared, based on published literature and expert opinion. The vignettes were validated by a MF patient expert and described typical MF patients with varying disease stage (IA-IVB) and skin burden, as assessed by the modified Severity Weighted Assessment Tool (mSWAT). Other included patient characteristics (age, Eastern Cooperative Oncology Group [ECOG] score) were informed by a patient registry. UK clinicians, working at key NHS lymphoma treatment centres (N=7), acted as respondents and completed the EQ-5D-5L questionnaire (proxy version 2) electronically for each vignette, responding as they believed MF patients would. Responses were converted into HSUVs using the UK value set. In every disease stage, HSUVs decreased with increasing mSWAT score. Similarly, for each mSWAT range HSUVs decreased as disease stage advanced. This demonstrates the effect of increasing skin burden and disease progression on HRQoL. Despite this, HSUVs associated with mSWAT score=0 were similar, regardless of disease stage (0.945 in Stage IA, 0.924 in Stage IB-IIA and 0.917 in Stage IIB-IV). The results of this investigation suggest that proxy-reporting via EQ-5D represents a potential option for generating HRQoL data, if published estimates are not available. Despite the small sample size and indirect elicitation of data, the finding that HRQoL decreases with increased mSWAT score is aligned with published literature.

Mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) epidemiology and treatment pathway in Spain: new insights for an accurate description.

BackgroundMycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) is a rare lymphoma localized in the skin. Due to its indolent nature and similarity to other skin conditions, diagnosis is often delayed or incorrect. Consequently, accurate calculations of incidence and prevalence are difficult to make. The treatment pathway taken by MF-CTCL patients can differ depending upon local healthcare systems, clinical policies and guidelines.AimsThis study aims to (1) provide an estimate for the prevalence of treated MF-CTCL patients in Spain, (2) describe the Spanish patient treatment pathways for MF-CTCL, including quantification of the distribution of patients between primary, secondary and tertiary care institutions, and (3) investigate and quantify the treatment preferences of physicians.MethodologyThis study employed primary market research methodologies to facilitate the collection of patient numbers and treatment practices from healthcare professionals (HCPs) and patients.LimitationsPoor diagnosis of MF-CTCL may mean that actual prevalence levels in the broader population are higher than those estimated by this analysis of treated patients. This study was reliant upon accurate reporting by HCPs of patient numbers and their personal treatment practices. The rarity of the condition means the patient sample size is relatively small and limits possible accuracy of the quantitative analyses of patient-derived data, although this is supplemented by HCP-derived data in the analysis.FindingsAround 75% of MF-CTCL patients in Spain report that the initial diagnosis by their general practitioner is incorrect. This is usually due to underestimation of severity or type of skin disease. Once they have been correctly diagnosed (usually by a dermatologist) in secondary care, the management of MF-CTCL is led by dermatologists. In 39% of patients, shared care teams are also involved in patient management. Following diagnosis, the majority of patient management is conducted by secondary or tertiary care centers.ConclusionsIncidence rates have increased in recent years, and possible reasons for this include improving levels of diagnosis. Survival in MF-CTCL has also increased over the last few decades. This trend appears to be reflected in the prevalence reported in this study, which is higher than suggested by some other estimates. However, it is still likely that there are further undiagnosed MF-CTCL patients in Spain due to the challenges of diagnosis at the primary care level.

Clinical potential of mechlorethamine gel for the topical treatment of mycosis fungoides-type cutaneous T-cell lymphoma: a review on current efficacy and safety data.

Nitrogen mustard is a chemotherapeutic agent that has a well-documented safety and efficacy profile in the treatment of cutaneous T-cell lymphoma. Development of nitrogen mustard formulations and treatment regimens has been studied extensively over the last 40 years. In the last 5 years, a new gel formulation has been developed that is associated with a decrease in delayed hypersensitivity reactions. The authors in this review found that while the gel formulation may result in a decrease of allergic contact dermatitis, this advantage has been replaced by a higher number of irritant contact reactions and a decrease in complete response rate. The gel formulation has a complete response rate of 13.8%, which is a decrease in efficacy when compared to aqueous-based preparations of similar concentrations.

Immunohistochemical staining for CD45R isoforms in paraffin sections to diagnose mycosis fungoides–type cutaneous T-cell lymphoma

The definitive diagnosis of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL) is difficult because a cumulative set of information is typically required: clinical features, histopathology, and special diagnostic tests (typically immunophenotyping and T-cell receptor gamma [TCRgamma] gene rearrangement). Fresh tissue is not always available for the special tests. We report a simple and readily available procedure evaluating the staining pattern on formalin-fixed, paraffin-embedded skin that can help with the diagnosis of patch/plaque stage MF. We reviewed 92 cases of MF or probable MF that had clinical information, immunophenotyping and TCRgamma gene rearrangement studies and that had been evaluated in our multidisciplinary lymphoma conference. We used antibodies to the isoforms of CD45, CD45RO for mature T cells and CD45RB for subsets of T cells. When atypical CD45RB-positive/CD45RO-negative cells were seen in nonspongiotic epidermis, the individuals had a high cumulative clinical and histologic score for MF. In contrast, 15 cases of known contact dermatitis showed a reactive pattern of both CD45RB- and CD45RO-positive cells in spongiotic epidermis. We compared the epidermal CD45RB-positive/CD45RO-negative staining pattern with CD7 deficiency by immunophenotyping and TCRgamma gene rearrangement, two commonly used methods in the diagnosis of MF. The epidermal CD45RB-positive/CD45RO-negative staining pattern is comparable and may be better in equivocal cases of possible MF. Therefore immunostaining for CD45RB and CD45RO on paraffin sections is a simple, reliable, and convenient modality in the diagnosis of MF.

Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma and Neutrophilic Dermatosis

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). Patients with limited patch and/or plaque disease have a normal life expectancy. Neutrophilic dermatosis (ND) may be associated with various hematologic disorders. However, its association with CTCL is exceptional and has been reported only twice with leukemic forms of CTCL. Three patients with MF developed ND resistant to conventional therapies and responsible for an impaired quality of life due to constitutional symptoms and painful cutaneous lesions. All patients underwent an aggressive treatment course despite their varying initial clinical stages of MF, and all experienced a fatal outcome less than 18 months after the onset of ND. The association of MF with ND is exceptional and carries a poor prognosis, but the pathophysiologic nature of this association remains unclear. It may involve neutrophil chemoattractant cytokine production by tumor cells. A triggering role of interferon alfa is also possible.

Woringer-Kolopp Disease (Localized Pagetoid Reticulosis) or Unilesional Mycosis Fungoides?

The controversial nosology of Woringer-Kolopp disease (localized pagetoid reticulosis, unilesional mycosis fungoides) is being clarified by the systematic immunophenotypic and immunogenetic examination of infiltrating lesional T lymphocytes. The clinical course and immunohistochemical characteristics of eight cases of Woringer-Kolopp disease are described. Lesions measured 0.8 x 0.5 to 16.0 x 15.0 cm. Histologically, all cases resembled mycosis fungoides-type cutaneous T-cell lymphoma and phenotypic analysis supported their designation as an epidermotropic T-cell process. Phenotypic aberrancy was not noted on immunohistochemical analysis of paraffin-embedded tissue. Three of four patients with available fresh-frozen tissue specimens demonstrated reduced or absent expression of CD7 (Leu-9) and/or Leu-8, while loss of the pan-T-cell markers CD2, CD3, and CD5 was not observed. Only in half these patients was a lesional predominance of CD4+ T-cells revealed. Germline DNA was detected in a lesional skin specimen obtained from one patient tested for T-cell receptor gene rearrangements. After treatment, the observation of disease-free periods ranging from 18 months to 17 years (mean, 5.9 years) reinforces the view that Woringer-Kolopp disease is a focal pathologic event with a favorable prognosis. No patient experienced a local recurrence or distant spread of the disease. This and previous studies suggest that Woringer-Kolopp disease is a unique, benign unilesional T-cell lymphoproliferative process with certain histologic and phenotypic similarities to both early epidemotropic mycosis fungoides-type cutaneous T-cell lymphoma and other T-cell lymphoproliferations.

Cutaneous T-cell lymphoma associated with HIV infection

Mycosis fungoides-type cutaneous T-cell lymphoma is uncommon in association with human immunodeficiency virus type 1 (HIV-1) infection. Reported patients have a high incidence of CD8+ T-cell lymphomas and erythroderma, are usually severely immunocompromised, and rapidly die. Chronic, more typical patch-plaque mycosis fungoides-type cutaneous T-cell lymphoma in association with HIV-1 infection has not been reported. We report two cases of stage 1B epidermotropic mycosis fungoides-type cutaneous T-cell lymphoma in HIV-1-infected men with no history of the acquired immunodeficiency syndrome. Clinical and laboratory data, including lesional immunophenotypic and immunogenotypic findings of two patients with HIV-1-associated cutaneous T-cell lymphoma, were studied. Immunohistochemical analysis of skin determined the lesional infiltrate of one patient to be CD8+ (Leu-2+), CD7- (Leu-9-), and Leu-8- with germline lesional skin and blood T-cell receptor genes. The other was CD4- (Leu-3+), CD2- (Leu-5-), CD7- (Leu-9-), and Leu-8- with beta-chain T-cell receptor gene rearrangement in lesional skin and blood. Circulating Sézary cells were not detected in either patient. Peripheral CD4/CD8 T lymphocyte numbers did not appear to correlate with cutaneous disease activity or the predominant lesional T-cell subtype. Both patients were responsive to standard therapies and have experienced prolonged survival in excess of that generally reported for HIV-1-associated systemic peripheral and cutaneous T-cell lymphomas. In the absence of severe immunodeficiency, HIV-1-infected patients with concomitant cutaneous T-cell lymphoma may follow a more typical slowly progressive course.

Complete remissions in psoralen and UV-A (PUVA)-refractory mycosis fungoides-type cutaneous T-cell lymphoma with combined interferon alfa and PUVA

Complete remissions in psoralen and UV-A (PUVA)-refractory mycosis fungoides-type cutaneous T-cell lymphoma with combined interferon alfa and PUVA

Mycosis fungoides-type cutaneous T-cell lymphoma arising before 30 years of age: Immunophenotypic, immunogenotypic, and clinicopathologic analysis of nine cases

Cutaneous T-cell lymphomas (CTCLs) rarely arise before 30 years of age; therefore the characteristics of these lymphomas are largely unknown. Our purpose was to assess the clinical and pathologic aspects of CTCL in young persons. We identified nine patients who had epidermotropic CTCL by 30 years of age and analyzed their lymphoma phenotypes and genotypes. The diagnosis of CTCL was made an average of 6 years after the reported onset of the lesion. Histologic examination revealed the mycosis fungoides (MF) form of CTCL, and none of the patients underwent conversion to nonepidermotropic or large-cell variants of CTCL. The immunophenotypes were typical of MF-type CTCL; seven of eight lymphomas tested were predominantly CD4+ although in only three were abnormal CD4/CD8 ratios present. All four cases tested were CD7- (Leu-9-), and seven of eight specimens tested exhibited deficient Leu-8 expression. The loss of one or more pan-T-cell markers was found in four of eight patients tested. Clonal beta-chain T-cell receptor gene rearrangements occurred in skin samples from four of eight tested cases. A persistent eruption, even in youths and young adults, should be thoroughly evaluated for possible CTCL.