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Current Treatment Options in Oncology Jan 2021While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a... (Review)
Review
While most patients with early-stage mycosis fungoides (MF) follow an indolent course, patients with advanced-stage MF/Sézary syndrome (SS) have a poor prognosis with a median survival of less than 5 years. Although there are a number of treatments currently available, achieving and maintaining a durable response remain challenging, especially in advanced-stage MF/SS. The choice of frontline therapy is dependent on the stage of disease. For early-stage MF, the treatment concept is to control skin lesions mainly by skin-directed therapies, such as topical therapies, phototherapies, and radiotherapies. For advanced-stage MF/SS, systemic treatments by biological or targeted therapies including bexarotene and interferon either alone or in combination are tried first, with more immunosuppressive chemotherapies being reserved for refractory or rapidly progressive disease. Recent improvements in biological or targeted therapies include brentuximab vedotin and mogamulizumab. When biopsy samples have 10% or more CD30-positive malignant cells, brentuximab vedotin, an anti-CD30 antibody conjugated to monomethyl auristin E, can be a desirable treatment option. For cases with blood involvement, mogamulizumab, an antibody binding to C-C chemokine receptor 4, is effective with high response rates. In the refractory setting, alemtuzumab, histone deacetylase inhibitors, pralatrexate, gemcitabine, and doxorubicin are considered as the treatment option. Because only allogeneic hematopoietic stem cell transplantation can offer a chance of cure with durable complete remission, advanced-stage patients with a markedly short life expectancy should be evaluated for eligibility. Given that there are few randomized controlled studies in the literature, it is necessary to investigate which therapy is preferable for each patient with MF/SS by comparative prospective trials.
Topics: Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Progression; Humans; Mycosis Fungoides; Neoplasm Grading; Neoplasm Staging; Prognosis; Sezary Syndrome; Skin Neoplasms; Treatment Outcome
PubMed: 33415447
DOI: 10.1007/s11864-020-00809-w -
Dermatologic Clinics Oct 2015This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides,... (Review)
Review
This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides, Sézary syndrome, and CD30+ lymphoproliferative disorders. Although these folate antagonists are traditionally viewed as antiproliferative cell cycle inhibitors, it is recognized that they inhibit DNA methylation, providing a rationale for their use as epigenetic regulators and cell proliferation inhibitors. The underlying mechanisms are outlined, key supporting data presented, followed by brief mention of recent mathematical modeling supporting the general superiority of combination therapy. Several novel examples involving folate antagonists are proposed.
Topics: Aminopterin; Antimetabolites, Antineoplastic; Apoptosis; DNA Methylation; Epigenesis, Genetic; Folic Acid Antagonists; Humans; Lymphoma, T-Cell, Cutaneous; Methotrexate; S Phase; Skin Neoplasms
PubMed: 26433846
DOI: 10.1016/j.det.2015.05.009 -
Archives of Dermatological Research Nov 2023Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the...
Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the progression of mycosis fungoides (MF).This study aims to examine the associations between the length of dupilumab treatment, age and sex, and the onset of MF.An institutional data registry and literature search were used for a retrospective cross-sectional study. Only patients with a diagnosis of MF on dupilumab for the treatment of AD and eczematous dermatitis were included.The primary outcome was the length of dupilumab exposure, age, sex, and the onset of MF. Linear correlations (Pearson) and Cox regression analysis were used to assess the correlation and the risk.A total of 25 patients were included in this study. Five eligible patients were identified at our institution. In addition, a PubMed review identified an additional 20 patients. At the time of MF diagnosis, the median age was 58, with 42% female. Disease history was significant for adult-onset AD in most patients (n = 17, 65.4%) or recent flare of AD previously in remission (n = 3, 11.5%). All patients were diagnosed with MF, and one patient progressed to Sézary syndrome while on dupilumab, with an average duration of 13.5 months of therapy prior to diagnosis. Tumor stage at diagnosis of MF was described in 19 of the cases and ranged from an early-stage disease (IA) to advanced disease (IV). Treatment strategies included narrow-band UVB therapy, topical corticosteroids, brentuximab, pralatrexate, and acitretin. Male gender, advanced-stage disease, and older age correlated significantly with the hazard of MF onset and a shorter time to onset during dupilumab treatment.Our results suggest a correlation between the duration of dupilumab treatment and the diagnosis of MF, the higher MF stage at diagnosis, and the shorter the duration of using dupilumab to MF onset. Furthermore, elderly male patients appeared to be more at risk as both male gender and older age correlated with a hazard of MF diagnosis. The results raise the question as to whether the patients had MF misdiagnosed as AD that was unmasked by dupilumab or if MF truly is an adverse effect of treatment with dupilumab. Close monitoring of these patients and further investigation of the relationship between dupilumab and MF can shed more light on this question .
Topics: Adult; Humans; Male; Female; Aged; Middle Aged; Cross-Sectional Studies; Retrospective Studies; Mycosis Fungoides; Dermatitis, Atopic; Antibodies, Monoclonal; Skin Neoplasms
PubMed: 37270763
DOI: 10.1007/s00403-023-02652-z -
Australian Prescriber Apr 2019
Review
PubMed: 31048945
DOI: 10.18773/austprescr.2019.020 -
Blood Mar 2017Peripheral T-cell lymphoma, not otherwise specified, is a broad category of biologically and clinically heterogeneous diseases that cannot be further classified into any... (Review)
Review
Peripheral T-cell lymphoma, not otherwise specified, is a broad category of biologically and clinically heterogeneous diseases that cannot be further classified into any other of the existing entities defined by the World Health Organization classification. Anthracycline-containing regimens, namely cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), nowadays represent the standard first-line treatment; for patients who achieve a satisfactory response, a consolidation by means of autologous stem cell transplantation may offer a greater chance of long-term survival. Several patients, however, display treatment refractoriness or relapse soon after obtaining a response, and just a few of them are suitable transplant candidates. This is why several new agents, with innovative mechanisms of action, have been investigated in this context: pralatrexate, romidepsin, belinostat, and brentuximab vedotin have been approved for relapsed and refractory peripheral T-cell lymphomas based on their activity, although they do not significantly affect survival rates. The incorporation of such new drugs within a CHOP backbone is under investigation to enhance response rates, allow a higher proportion of patients to be transplanted in remission, and prolong survival.
Topics: Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Peripheral
PubMed: 28115372
DOI: 10.1182/blood-2016-08-692566 -
Expert Opinion on Biological Therapy Sep 2017T-cell lymphoma is a relatively rare hematologic malignancy that accounts for 10-20% of non-Hodgkin lymphomas. Treatment strategies for T-cell lymphomas are different... (Review)
Review
T-cell lymphoma is a relatively rare hematologic malignancy that accounts for 10-20% of non-Hodgkin lymphomas. Treatment strategies for T-cell lymphomas are different from that for B-cell lymphomas and have poor prognoses. Among various subtypes of T-cell lymphomas, adult T-cell leukemia-lymphoma (ATL) has the worst prognosis. To achieve further improvement in the treatment outcome of T-cell lymphomas, several novel agents such as brentuximab vedotin, lenalidomide, romidepsin, and pralatrexate are actively being studied. Mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, is one of the promising agents for CCR4-positive T-cell lymphomas, especially for ATL. Areas covered: First, basic information about the current treatment strategy of T-cell lymphomas including ATL is described. Then, the authors discuss the current clinical development of mogamulizumab and its clinical implications for T-cell lymphomas. Expert opinion: Mogamulizumab has potent clinical efficacy against CCR4-positive T-cell lymphomas, especially against ATL. Among various toxicities associated with mogamulizumab, skin eruptions are the most significant. Although there are several effective competitors, mogamulizumab has a unique mechanism and is expected to be a key agent for treating CCR4-positive T-cell lymphomas, especially ATL.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Clinical Trials as Topic; Half-Life; Humans; Immunohistochemistry; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, T-Cell; Neoplasm Recurrence, Local; Receptors, CCR4; Skin Diseases; Treatment Outcome
PubMed: 28649848
DOI: 10.1080/14712598.2017.1347634 -
Biomolecules & Therapeutics May 2021Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global...
Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.
PubMed: 33731494
DOI: 10.4062/biomolther.2021.032 -
Oncology (Williston Park, N.Y.) May 2022The peripheral T-cell lymphomas (PTCLs) are a notoriously diverse family of non-Hodgkin lymphomas with generally aggressive biology. Clinical management is challenging...
The peripheral T-cell lymphomas (PTCLs) are a notoriously diverse family of non-Hodgkin lymphomas with generally aggressive biology. Clinical management is challenging given a largely inadequate literature base comprised of few randomized trials and heterogeneous observational reports. Herein, we provide an account of our practice in the treatment of the 3 most common nodal PTCLs: PTCL, not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma (ALCL). In the up-front setting, we employ anthracycline-based induction, with the incorporation of brentuximab vedotin for all those with ALCL and consideration in those with other CD30-expressing PTCLs based on improved progression-free and overall survival in the absence of additional toxicity in the ECHELON-2 trial. We strongly consider high-dose therapy with autologous stem cell rescue in first complete remission. In the relapsed or refractory (R/R) setting, we often look to clinical trials or choose from 4 FDA-approved single agents-belinostat, brentuximab vedotin, romidepsin, and pralatrexate-based on tumor phenotype and side-effect profiles. Our goal in the R/R setting is achievement of complete remission followed by allogeneic transplant with curative intent in appropriate candidates or long-term disease control in others. Numerous investigational agents are advancing through trials and have potential to alter standards of care in the near future.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brentuximab Vedotin; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Peripheral; Transplantation, Autologous
PubMed: 35576176
DOI: 10.46883/2022.25920960 -
The Journal of Dermatology Feb 2022Cutaneous lymphoma is generally treated with skin-directed therapies (SDT) during the early and localized stages. For the refractory or advanced stages, systemic... (Review)
Review
Cutaneous lymphoma is generally treated with skin-directed therapies (SDT) during the early and localized stages. For the refractory or advanced stages, systemic therapies are used. Previously, retinoids and interferons were used for SDT-resistant cases. Only a few chemotherapy options were available for more advanced disease. In recent years, many novel agents have been introduced and the strategy for systemic therapy has changed, especially for cutaneous T-cell lymphoma (CTCL). For SDT, helical tomotherapy, a new radiation modality, has been drawing attention as an option for radiotherapy. Targeted therapies such as histone deacetylase inhibitors, mogamulizumab, brentuximab vedotin, and denileukin diftitox are new treatment options. Chemotherapy agents such as gemcitabine and pralatrexate have been introduced; they are expected to have meaningful efficacy as monotherapy. Allogeneic hematopoietic stem cell transplantation is still considered for young patients with advanced CTCL as the only potentially curative treatment.
Topics: Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Cutaneous; Retinoids; Skin Neoplasms
PubMed: 34958516
DOI: 10.1111/1346-8138.16289