36 research outputs found
The PROVe study: US real-world experience with chlormethine/mechlorethamine gel in combination with other therapies for patients with mycosis fungoides cutaneous T-cell lymphoma
BACKGROUND: Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking.
OBJECTIVE: Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting.
METHODS: This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA-IB disease receiving chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire.
RESULTS: In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (chlormethine + topical corticosteroids + other) and 45.1% (patients receiving chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores.
CONCLUSIONS: This real-world study confirmed that chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life
What Does the Future Hold for Biomarkers of Response to Extracorporeal Photopheresis for Mycosis Fungoides and Sézary Syndrome?
Extracorporeal photopheresis (ECP) is an FDA-approved immunotherapy for cutaneous T-cell lymphoma, which can provide a complete response in some patients. However, it is still being determined who will respond well, and predictive biomarkers are urgently needed to target patients for timely treatment and to monitor their response over time. The aim of this review is to analyze the current state of the diagnostic, prognostic, and disease state-monitoring biomarkers of ECP, and outline the future direction of the ECP biomarker discovery. Specifically, we focus on biomarkers of response to ECP in mycosis fungoides and Sézary syndrome. The review summarizes the current knowledge of ECP biomarkers, including their limitations and potential applications, and identifies key challenges in ECP biomarker discovery. In addition, we discuss emerging technologies that could revolutionize ECP biomarker discovery and accelerate the translation of biomarker research into clinical practice. This review will interest researchers and clinicians seeking to optimize ECP therapy for cutaneous T-cell lymphoma
Clonal T-Cell Receptor γ-Chain Gene Rearrangements in Differential Diagnosis of Lymphomatoid Papulosis From Skin Metastasis of Nodal Anaplastic Large-Cell Lymphoma
Targeting the CD47-SIRPα Axis: Present Therapies and the Future for Cutaneous T-cell Lymphoma
The loss of CD47 on aging cells serves as a signal to macrophages to eliminate the target. Therefore, CD47 is a “do-not-eat-me” sign preventing macrophagal phagocytosis via interaction with its ligand SIRPα. Malignant lymphocytes of mycosis fungoides and Sézary syndrome express CD47 highly, thus, being ideal candidates for targeted anti-CD47 therapies. The classes of current anti-CD47-SIRPα therapeutic molecules present in a large variety and include monoclonal antibodies against CD47 and SIRPα, bioengineered SIRPα proteins, miRNAs, and bispecific antibodies. We provided a detailed analysis of all available investigational drugs in a contest of cutaneous T-cell lymphoma. A combination of blockade of the CD47-SIRPα axis and secondary targets in the tumor microenvironment (TME) may improve the clinical efficacy of current immunotherapeutic approaches. We evaluated the possible combination and outlined the most promising one
Romidepsin Controls Chronic Lymphocytic Leukemia in a Patient with Mycosis Fungoides
Romidepsin belongs to a class of medications called histone deacetylase inhibitors and is currently approved for treatment of cutaneous and peripheral T-cell lymphomas. Romidepsin was previously investigated for the treatment of chronic lymphocytic leukemia (CLL), and demonstrated potential benefit, but interest in its use declined following phase I clinical trials that showed poor tolerance of a significant side effect profile. We presented a patient with a history of stage II CLL, referred to dermatology for treatment of new-onset of mycosis fungoides (MF), who was treated with romidepsin over seven months. The patient achieved a partial response with 50% decrease in body surface area occupied by MF, thinning of remaining plaques, and near complete response in his CLL. His absolute lymphocyte count remained within the normal range for four months following discontinuation of romidepsin. Side effects were well-tolerated and did not limit therapy. Current literature on romidepsin is reviewed and compared to existing treatments for CLL
A Mechanistic Study of δ-Aminolevulinic Acid-Based Photodynamic Therapy for Cutaneous Leishmaniasis
CD5+ Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type, Presenting as an Asymptomatic Nodule
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is a rare and aggressive variant of primary cutaneous lymphoma that typically expresses B cells as well as MUM1/IRF4, BCL2, and FOXP1, whereas BCL6 may be present or undetectable. We present a case of CD5+ PCDLBCL-LT presenting as a 6 mm pink-bluish nodule on the mid-left thigh, which was concerning for basal cell carcinoma. The histological examination reveals the presence of an intradermal proliferation of large, atypical CD5+, CD20+ BCL2+, BCL6+, MUM-1+, and Cyclin-D1+ lymphocytes in a nodular, diffuse interstitial and perivascular distribution. Because the patient presented with a small, single nodule, the systemic treatment of multiagent chemotherapy was avoided and localized electron beam radiation therapy with rituximab was initiated instead, achieving complete response. Early identification of PCDLBCL-LT is key for maximal therapeutic benefit and prognosis; it is important to consider PCDLBCL-LT on the differential when evaluating small, single nodules on the lower extremities of elderly patients
Optimization of Topical Photodynamic Therapy With 3,7-bis(di-n-butylamino)Phenothiazin-5-ium Bromide for Cutaneous Leishmaniasis
Background And Objective: Photodynamic therapy (PDT) has evolved as a promising therapeutic measure for the treatment of cutaneous leishmaniasis (CL). In particular, phenothiazine compounds have demonstrated efficacy for PDT of CL. The objective of our present study is to define the use of a new specific phenothiazine photosensitizer, 3,7-bis(di-n-butylamino)phenothiazin-5-ium bromide (PPA904) applied topically as a cream to treat CL. Materials And Methods: To establish the optimal conditions for this treatment, we compared two different ways to improve current regimens of PDT with PPA904 cream (500 mu M of PPA904 in Unguentum M) by changing the duration of topical application, and by administration of several consecutive PDT procedures. An initial regimen recommended by the manufacturer (Photopharmica Co. Ltd., Leeds, UK) was maintained as a control: the cream was applied topically for 30 minutes at a final concentration of PPA904 at 500 mu M, and the designated treatment area was irradiated with a broad band light source of 665 +/- 15 nm at a fluence of 50 J/cm(2) (50 MW/cm(2)). Results: The best curative PPA904-PDT regimen was achieved under the conditions of a longer duration of topical application time (90 minutes) and several (three) consecutive treatments with 4-day intervals between treatments. The mechanisms responsible for such improvements (kinetics of drug penetration, depth of necrosis of the CL lesions after PDT, and daily changes in the parasitic load after PDT) are discussed in the present study. Conclusion: Topical PPA904-PDT, implemented as described above, is a promising treatment for CL, and clinical studies will be initiated to establish efficacy in humans